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In order to have a tool to empirically test the ideas derived from a theoretical model, we extended a protocol for evaluation of episodic-like memory in rats, based on the triad "what, where, context" for definition of memories. As with the computational model, our intention was for the animal being tested to store a specific number of object-place-context configurations as different memories, which would then be retrievable from cues. The aim of this work was to evaluate the influence of the number of configurations to be memorized on the performance of the task. Sixty-five Wistar male rats were evaluated. In accordance with previous work, for two configurations, the recognition index was indicative of recognition of the element mismatching the original memory (mean = 0.28; SEM = 0.12). The recognition index for three configurations was lower (mean = 0.15; SEM = 0.10), evidencing less recall with increasing requirements. The results also showed a trend toward recognition of novelty for the first and the last memory when evaluating three configurations (a "U" shape in the exploratory preference's curve), showing the primacy and recency effects typical of memory both in humans and animals. Nonetheless, the data presented a high inter-subject variability which makes the test non-robust for small groups. However, if used before and after a treatment for a same subject, we suggest that the protocol presented in this work can be a useful behavioral test for the evaluation of episodic-like memory in rats in terms of a variable task demand.

Since the nervous system has limited self-repair capability, a great interest in using stem cells is generated to repair it. The adipose tissue is an abundant source of stem cells and previous reports have shown the differentiation of them in neuron-like cells when cultures are enriched with growth factors involved in neurogenesis. Regarding this, it could be thought that a functional parallelism between neurogenesis and neuronal differentiation of human adipose stem cells (hASCs) exists. For this reason, we investigated the putative involvement of Notch and Wnt pathways in neuronal differentiation of hASCs through real-time PCR. We found that both Wnt and Notch signaling are present in proliferating hASCs and that both cascades are downregulated when cells are differentiated to a neuronal phenotype. These results are in concordance with previous works where it was found that both pathways are involved in the maintenance of the proliferative state of stem cells, probably through inhibition of the expression of cell-fate-specific genes. These results could support the notion that hASCs differentiation into neuron-like cells represents a regulated process analogous to what occurs during neuronal differentiation of NSCs and could partially contribute to elucidate the molecular mechanisms involved in neuronal differentiation of adult human nonneural tissues.

Stem cells were derived from hatched blastocyst-stage mouse embryos of the C57BL/6 strain employing a knockout serum replacement instead of the traditional fetal calf serum, thereby avoiding the use of immunosurgery. Although fetal calf serum was not good for isolation of stem cells, a combination of this serum plus knockout serum increased the expansion rate of the cell culture. The derived cells were capable of maintaining an undifferentiated state during several passages, as demonstrated by the presence of alkaline phosphatase activity, stage-specific embryonic antigen 1 (SSEA-1), and octamer binding protein 4 (Oct-4). Suspension culture in bacteriological dishes gave better results than the hanging drop method for differentiation by means of embryoid body formation. Mouse embryonic stem cells showed spontaneous differentiation into derivatives of the 3 germ layers in culture media supplemented with fetal calf serum but not with knockout serum.

The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N=16 pairs; males: N=12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N=6 pairs; males: N=6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p

Bioartificial liver devices are alternative therapies for patients suffering from acute hepatic failure or metabolic defects. Here, we show a bioartificial device, developed with a cartridge used for pediatric hemofiltration and spheroids of porcine hepatocytes housed in the extracapillary space of the cartridge. The cartridge was attached to a robotic arm that supplied a continuous, oscillatory movement. It was connected through the capillary circulation to a neonatal membrane oxygenator contain-ing human blood supplemented with ammonium and diazepam. A decrease in ammonium concentration was observed, reaching an almost 70% decrease upon 9 h of operation. In addition, urea was detected and diazepam metabolism proved from the fourth hour of operation. It is worth mentioning that the system described was assembled with commercially available components for current clinical use. The setup may be done in a short period, thus eliminating long-term culture times and the need for cell anchoring to matrices.

Trypanosoma cruzi , the causative agent of Chagas' disease, induces transient thymic aplasia early after infection—a phenomenon that stills lacks a molecular explanation. The parasite sheds an enzyme known as trans -sialidase (TS), which is able to direct transfer-sialyl residues among macromolecules. Because cell-surface sialylation is known to play a central role in the immune system, we tested whether the bloodstream-borne TS is responsible for the thymic alterations recorded during infection. We found that recombinant TS administered to naive mice was able to induce cell-count reduction mediated by apoptosis, mimicking cell subsets distribution and histologic findings observed during the acute phase of the infection. Thymocytes taken after TS treatment showed low response to Con A, although full ability to respond to IL-2 or IL-2 plus Con A was conserved, which resembles findings from infected animals. Alterations were found to revert several days after TS treatment. The administration of TS-neutralizing Abs to T. cruzi -infected mice prevented thymus alterations. Results indicate that the primary target for the TS-induced apoptosis is the so-called “nurse cell complex”. Therefore, we report here supporting evidence that TS is the virulence factor from T. cruzi responsible for the thymic alterations via apoptosis induction on the nurse cell complex, and that TS-neutralizing Abs elicitation during infection is associated with the reversion to thymic normal parameters.

The use of exogenous matrices has been described as an essential component in securing the viability and functionality of hepatocytes in vitro whether cultured for extracorporeal devices or cell transplantation. Here we report on the in vitro culture of porcine hepatocytes in polystyrene tissue-culture flasks without exogenous matrices showing adequate attachment and viability. Cell proliferation was evidenced by uptake of 5-bromo-2'-deoxyuridine, with peaks at Days 2 (19.7 +/- 8.5%), 15 (20.8 +/- 3.3%), and 35 (21.4 +/- 0.3%). Detoxification capacity was assessed by determination of monoethylglycinexylidide, a product of lidocaine metabolism (highest value 156.5 +/- 10.1 ng/ml at Day 4), and by diazepam clearance (maximum clearance 66.2% at Day 6). Diazepam metabolite levels were highest at Day 4 both for temazepam and oxazepam (6.5 +/- 0.1 and 0.10 +/- 0.01, respectively). These results suggest that the need for an exogenous matrix to achieve sustained proliferative activity and differentiated hepatocyte function should not necessarily be considered a sine qua non condition.

Fulminant hepatic failure is an important cause of morbidity and mortality in intensive care units. Conventional therapies are not sufficiently effective. Liver transplantation may be life saving, but a "bridge therapy" is needed until transplantation is performed. Hepatic extracorporeal xenohemodiafiltration (XHDF) is aimed at the transitory support of a patient with fulminant hepatic failure. The first clinical case of XHDF is presented. The system consisted of cross-circulation between a porcine liver and a patient with fulminant liver failure through a polyacrylonitrile membrane. The procedure lasted for 5 hours and produced hemodynamic, biochemical, and metabolic improvements. Intracranial pressure decreased from 34 to 5 cm H2O, serum ammonia fell from 673 to 370 ng/dl, lactic acid from 11 to 5.3 mmol/L, and bilirubin from 7.4 to 2.5 mg/dl. Hemodynamic values were maintained stable throughout the procedure. The patient was able to undergo transplantation and remains alive 11 months later. XHDF is a clinical experimental method that can constitute an alternative clinical therapy to support patients with fulminant hepatic failure until an organ is available for transplantation.

Trypanosoma cruzi, the etiologic agent of Chagas' disease, expresses trans-sialidase, an enzyme able to direct transfer of sialyl residues among macromolecules. The enzyme is shed and can be detected in blood during the acute phase of the disease. Several alterations of the immune response and apoptosis of cellular components of the immune system are observed early in the infection. The possible involvement of bloodstream trans-sialidase on these events was analyzed here. The enzyme induced apoptosis in cells of the immune system in the spleen, thymus, and peripheral ganglia. Both natural and recombinant trans-sialidases induced apoptosis to a similar extent. No effect was detected when enzymatically inactive recombinant molecules were used. In dose-response assays, apoptosis was observed even when an amount of trans-sialidase was administered that was enzymatically undetectable in blood. These findings strongly suggest a role for sialic acid mobilization in T. cruzi-induced apoptosis of immune system cells.

The conversion of differentiated cells into insulin-producing cells is a promising approach for the autologous replacement of pancreatic cells in patients with type 1 diabetes (T1D). At present, cellular reprogramming strategies encompass ethical problems, epigenetic failure or teratoma formation, which has prompted the development of new approaches. Here, we report a novel technique for the conversion of skin fibroblasts from T1D patients into insulin-expressing clusters using only drug-based induction. Our results demonstrate that skin fibroblasts from diabetic patients have pancreatic differentiation capacities and avoid the necessity of using transgenic strategies, stem cell sources or global demethylation steps. These findings open new possibilities for studying diabetes mechanisms, drug screenings and ultimately autologous transgenic-free regenerative medicine therapies in patients with T1D. Fil: Pereyra Bonnet, Federico Alberto. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gimeno, Maria Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Argumedo, Nelson R.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Ielpi, Marcelo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Cardozo, Johana A.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Giménez, Carla Alejandra. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hyon, Sung Ho. Hospital Italiano; Argentina Fil: Balzaretti, Vilma Teresa. Hospital Italiano; Argentina Fil: Loresi, Monica Alejandra. Hospital Italiano; Argentina Fil: Fainstein Day, Patricia. Hospital Italiano; Argentina Fil: Litwak, Sara Alejandra. Hospital Italiano; Argentina Fil: Argibay, Pablo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Several glycoproteins in mammalian brains contain α2,8-linked disialic acid residues. We previously showed a constant expression of disialic acid (DiSia) in the hippocampus, olfactory bulb and cortex, and a gradual decrease of expression in the cerebellum from neonatal to senile mice. Previous publications indicate that neurite extension of neuroblastoma-derived Neuro2A cells is inhibited in the presence of DiSia antibody. Based on this, we treated Neuro2A cell cultures with RNA interference for ST8SiaIII mRNA, the enzyme responsible for DiSia formation. We observed that neurite extension was inhibited by this treatment. Taking this evidence into consideration and the relationship of the cerebellum with learning and memory, we studied the role of DiSia expression in a learning task. Through delivery of pST8SiaIII into the brains of C57BL/6 neonatal mice, we inhibited the expression of ST8SiaIII. ST8SiaIII mRNA and protein expressions were analyzed by real-time PCR and western blot, respectively. In this work, we showed that pST8SiaIII-treated mice presented a significantly reduced level of ST8SiaIII mRNA in the cerebellum (p < 0.01) in comparison to control mice at 8 days after treatment. It is also noted that these levels returned to baseline values in the adulthood. Then, we evaluated behavioural performance in the T-Maze, a learning task that estimates procedural memory. At all ages, pST8SiaIII-treated mice showed a lower performance in the test session, being most evident at older ages (p < 0.001). Taken all together, we conclude that gene expression of ST8SiaIII is necessary for some cognitive tasks at early postnatal ages, since reduced levels impaired procedural memory in adult mice. Fil: Rinflerch, Adriana Raquel. Hospital Italiano. Instituto de Cs.basicas y Medicina Experimental; Argentina Fil: Burgos, Valeria Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Ielpi, Marcelo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Ojea Quintana, Ignacio María. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Hidalgo, Alejandra M.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Loresi, Monica Alejandra. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Argibay, Pablo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

This study was designed to analyze the effect of hippocampal neurogenesis on the spatial maps of granule cells. Accordingly, we developed and improved an artificial neural network that was originally proposed by Aimone. Many biological processes were included in this revised model to improve the biological relevance of the results. We proposed a novel learning-testing protocol to analyze the activation of encoding place cells across contexts and over time in the dentate gyrus. We observed that, regardless of the presence of neurogenesis, the quantity and morphology of the place fields were represented in the same manner by granule cells. Additionally, we observed that neurogenesis was an effective mechanism for reducing the degree of rate remapping that occurred in the place fields of the granule cells.

OBJECTIVE To determine whether small intestine submucosa has the same regenerative capacity when urethroplasty is performed in injured urethras. METHODS Our experiment was conducted in 30 New Zealand male rabbits, all of which had urethral injury. One month after the injury, the animals were randomized into a control group or a group with onlay urethroplasty with small intestine submucosa. The animals were euthanized at 2, 4, 12, 24, and 36 weeks after urethroplasty, and their urethras were removed for histologic and immunohistochemical examination. Before the scheduled euthanasia, urethrography and cystoscopy were performed. RESULTS After 2 weeks, there was evidence of a continuous monolayer of stratified epithelial cells and absence of smooth muscle fibers. One month later, the epithelium showed no changes from the previously observed features, but some smooth muscle fibers (representing newly formed vessels) became apparent. After 3 months, the graft showed increased concentration of smooth muscle fibers. After 6 and 9 months, the density of smooth muscle cells remained unchanged. Fiber arrangement was irregular, particularly at the anastomosis site. Epithelial and smooth muscle phenotypes were confirmed by immunohistochemistry using anti-pan-citokeratin (AE1/AE3) antibodies and anti-a-smooth muscle actin, respectively. CONCLUSION Small intestine submucosa promotes regeneration in traumatized urethras, with slightly delayed epithelialization and abnormal distribution of smooth muscle. Urethral damage caused by trauma interferes with the normal healing process. Fil: Villoldo, Gustavo Martin. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Loresi, Monica Alejandra. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Giudice, Carlos. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Damia, Oscar. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Moldes, Juan Manuel. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Debadiola, Francisco. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Barbich, Mariana. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina Fil: Argibay, Pablo. Hospital Italiano. Instituto Universitario - Escuela de Medicina. Departamento de Ciencias Básicas. Area Inmunología de Transplantes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

It is known that disialic acids (diSia) are present in the mammalian brain. However, the precise anatomical distribution and the chronology of its expression along life are not well studied yet. It is accepted that the transfer of diSia in the brain is mediated mainly by the enzyme ST8Sia III (α2,8-sialyltransferase III). We studied the expression of diSia glycoepitopes and of the ST8Sia III gene in different structures of the mouse brain at different postnatal stages by immunohistochemistry and real-time polymerase chain reaction, respectively. C57BL/6 mice of different stages were used. Samples of hippocampus, olfactory bulb, cortex and cerebellum were processed for studies of molecular biology and immunohistochemistry. Histological analysis revealed an important decrease in diSia labeling in the senile cerebellum compared with other structures and stages (P ≪ 0.001). In concordance with these results, a significant decrease in ST8Sia III gene expression was found in the cerebellum of senile animals (P 0.001). These results suggest that diSia are constantly expressed but with differential expression in various areas of the mouse central nervous system. On the other hand, the concordance in the decreased expression of ST8Sia III and the diSia epitope in the cerebellum of senile animals suggest a role of diSia in this structure or, inversely, an influence of aging on the expression of diSia in the cerebellum. Further research in that direction could elucidate the roles of diSia in brain function in health and disease.

The glycan chains of glycoconjugates play important roles in cell-cell and cell-matrix interactions. In the CNS, previous studies on learning and memory suggest the importance of oligosaccharides attached to glycoconjugates in the modulation of synaptic connections. We studied the hippocampal glycan distribution of rats subject to an inhibitory avoidance task. The expression of glycans was examined by lectin-histochemistry using Vicia villosa lectin (VVL) for terminal alpha/beta N-acetylgalactosamine (alpha/beta GalNAc); Galanthus nivalus lectin (GNL) for terminal mannose alpha-1,3 (Man alpha-1,3); Peanut agglutinin (PNA) for galactose beta-1,3N-acetylgalactosamine (Gal beta-1,3 GalNAc); Erythrina cristagalli lectin (ECL) for galactose beta-1,4 N-acetylglucosamine (Gal beta-1,4 GlcNAc); Sambucus nigra lectin (SNA) for sialic acid alpha-2.6 galactose (SA alpha-2,6 Gal); Maackia amurensis lectin II (MAL II) for sialic acid alpha-2,3 (SA alpha-2,3); Wheat germ agglutinin (WGA) for terminal N-acetylglucosamine with/ without sialic acid (GlcNAc wo SA); succynilated WGA (sWGA) for terminal N-acetylglucosamine without sialic acid (terminal GlcNAc without SA); Griffonia simplicifolia lectin II (GSL II) for terminal alpha/beta N-acetylglucosamine (alpha/beta GlcNAc terminal); and Lotus tetragonolobus lectin (LTL) alpha-fucose. Two groups of 10 animals were examined: non-trained (Control) and Trained rats. ECL, sWGA and GSL II were negative for both groups in all the hippocampal subfields studied. For both groups, VVL was negative in CA4 and granular cells of the Dentate Gyrus (DG) and LTL was negative in the CA4 subfield. Expression of alpha/beta GalNAc, alpha-fucose and GlcNAc in other hippocampal subflields was positive, with no differences between groups. However, expression of Man alpha-1,3 was significantly higher in the CA1, CA2, CA3, and CA4 subfields in the Trained group. On the other hand, expression of Gal beta-1,3 GalNAc was significantly low in CA4 and DG in the Trained group. In conclusion, the results here presented indicate that the exposure of rats to an associative behavioral paradigm related to declarative memory, involves some regulatory mechanism/s for the differential patterns of glycan expression.

Although a putative role has been attributed to inflammation in the pathogenesis of depressive disorders, the relationship of prostaglandins, known mediators of inflammation, and depression has not been elucidated. Clomipramine is an antidepressive drug with a pro-depressive paradoxical effect in adult rats when administrated neonatally. Using this effect as a model of depression, we investigated the differential expression of the cyclooxygenase (COX-2) gene in rat brains. Rats injected neonatally with clomipramine showed depressive-like symptoms in adulthood, as well as decreased levels of the brain-derived neurotrophic factor (BDNF) and a quantitative differential expression of the COX-2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As evidenced, the relationship between a key enzyme in the prostaglandin synthesis and biological and behavioral depression-like changes opens an interesting line of investigation regarding the molecular bases of depression and its potential treatment through immunomodulatory drugs.

1. Vascular endothelial growth factor (VEGF) has been related with several brain functions such as angiogenesis, neuroprotection, and neurogenesis. 2. We studied the mRNA expression of the two most important isoforms of VEGF (VEGF120 and VEGF164) as well as one type of VEGF receptors, neuropilins (NRP), during maturation in the rat brain using real-time PCR. 3. Today, real-time PCR is the method of choice for rapid and reliable quantification of mRNA transcription. 4. VEGF120 has little changes in its expression between P5 and P30. 5. However, VEGF164 increased its expression 2-folds at P15 in comparison to P5, remaining at this level in the adult brain (P30). 6. Both types of NRP, NRP-1 and NRP-2, which only bind VEGF164, increased their expression about 2-folds only at P30, at levels similar to those observed for VEGF164.

Chiefly an intracellular parasite, Trypanosoma cruzi has a transient blood-borne stage (trypomastigote), the acute phase of Chagas' disease, during which surface trans-sialidase is expressed and shed by the parasite. It's immunosuppressive through the induction of apoptosis. Herein, we investigated the role of trans-sialidase as an immune modulator of allo- and xenoreactions. Trans-sialidase strongly inhibited human lymphocyte proliferation; a role for the interleukin-2 receptor CD25 was suggested by flow cytometry. These results may have implications both for the pathogenesis of Chagas' disease and for transplantation immunology.

In fulminant liver failure (FLF) there is need for support as a bridge to liver transplantation. Based on the concepts of hemofiltration and xenotransplantation, the authors present a model of liver support in FLF. The authors performed a portacaval shunt and ligature of the hepatic artery in 12 pigs. In six pigs (Group A) continuous hemofiltration through a polyacrylonitrile membrane was performed. Six isolated dog's livers were catheterized through the portal vein and perfused with autologous erythrocytes, albumin, and electrolytes in a closed circuit. With the use of the auxiliary liver, the circuit was connected to one of the lateral outlets of the hemofilter, while the other lateral outlet was connected to the portal vein through the pump. Thus, a polyacrylonitrile exchange membrane was created between the blood of the pig with FLF and the auxiliary liver's circulation. In Group B (controls), six pigs were connected directly to the auxiliary liver through a pump. In Group A, the auxiliary liver worked for 8 hr, without evidence of macroscopic or histologic damage. Lactic acid and ammonia levels improved: lactic acid, 8.2 +/- 6 mmol/L to 1.6 +/- 1 mmol/L; ammonia 487 +/- 110 micrograms/dl to 117 +/- 13 micrograms/dl, p0.1. The lidocaine clearing (MEGX) test results remained at functional levels (90 ng/ml) at the end of the perfusion. In Group B, the perfusion was discontinued at 60 +/- 15 min because of evidence of necrosis of the auxiliary liver. Lactic acid levels increased from 8.19 +/- 1.1 mmol/L to 13 +/- 4 mmol/L, ammonia levels remained high (390 +/- 15 micrograms/dl to 480 +/- 80 micrograms/dl), and the MEGX test results showed levels below functional activity by the end of the perfusion (45 +/- 30 ng/ml). The authors conclude that the concept of xenohemodiafiltration based on the interposition of a polyacrylonitrile membrane between a xenograft and an animal in FLF is adequate to support functions of detoxification and could be used in the future in the support of patient with FLF.

Chagas' disease is a chronic, debilitating, multisystemic disorder that affects millions of people in Latin America. The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, has a large number of O-glycosylated Thr/Ser/Pro-rich mucin molecules on its surface (TcMuc). These mucins are the main acceptors of sialic acid and have been suggested to play a role on various host-parasite interactions, such as adhesion to macrophages, protection from complement lysis, and immunomodulation of the immune response mounted by the host. To observe the immunologic effect obtained by the heterologous expression of a TcMuc gene in higher eukaryotic cells exposed to xenogeneic lymphocytes, we developed a strategy based on the transfection of a known T. cruzi mucin gene (TcMuc-e2) into Vero cells. In contrast to the brisk proliferation and activation of human lymphocytes observed at 3, 4, and 5 days induced by normal Vero cells, neither proliferation nor significant activation of human lymphocytes was observed with TcMuc-e2-transfected Vero cells. This TcMuc-e2 mucin-induced suppression of T cell response can be reversed by the addition of exogenous IL-2. In addition it was demonstrated that the immunosuppressive reaction was not related to the induction of an important degree of apoptosis in human lymphocytes. Posttranslational modification are required for the inhibitory effect that TcMuc-e2 exerts when transfected to Vero cells. O-glycosylation and sialylation are required to obtain the immunomodulatory effect as assessed by O-sialoglycoprotease and neuraminidase treatments. These results are consistent with other studies showing that surface glycoconjugates from T. cruzi and mammalian cells can induce an inhibition of the immune response.