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In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3+ cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161+ T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161+ T cells; upregulation of CD69 was observed on both CD161− and CD161+ T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN- γ but no IL-4, IL-5 and IL-13 by CD161+ T cells in all groups; upon polyclonal stimulation, there were more CD161+ T cells producing IFN- γ and less CD161− T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161+ T cells are activated and are able to produce predominantly IFN- γ but no Th2 cytokines. We hypothesize that during an asthma attack, IFN- γ produced by CD161+ T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks. [ABSTRACT FROM AUTHOR]

Between December 1993 and November 2001, 30 patients with chronic myeloid leukemia who relapsed after stem cell transplantation were studied. Seventeen patients were not treated before donor lymphocyte infusion (DLI), eight patients received interferon-α (IFN-α), and five underwent chemotherapy. The method of DLI was the bulk dose regimen. The median time between DLIs was 6 weeks. The median number of infusions was three; the median time from transplant to relapse was 17 months and from relapse to DLI 2 months. Eleven patients (37%) were in molecular/cytogenetic relapse, 14 (47%) in chronic phase, and five (16%) in accelerated or blastic phase. Seventeen patients (57%) developed acute graft-versus-host disease (GVHD). Chronic GVHD was observed in 15 of 24 (62%) patients. Four (13%) patients developed cytopenia after a median of 30 days. Nineteen (63%) patients achieved response, 15 of them developed GVHD. The response rate according to the disease phase was molecular or cytogenetic relapse: 91%, chronic phase: 57%, and accelerated or blastic phase: 20%. The median time to response was 6 months. Patients treated with IFN-α or no treatment as well as those who were in molecular/cytogenetic relapse and those who received a CD3+ cell dose <1×108/kg and CD4+ <8×107/kg had better survival. We conclude that patients who receive lower doses of lymphocytes have better survival. In some patients IFN-α seems to be a good choice to potentiate the graft-versus-leukemia (GVL) effect. [ABSTRACT FROM AUTHOR]

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Previous studies have demonstrated that patients with chronic brucellosis have increased numbers of peripheral blood CD8+ T lymphocytes. Now, we evaluate the response of individual T lymphocytes to B. abortus RB51 saline extracted antigen (RCM-RB51) stimulation, in order to determine whether there is preferential proliferation of a particular T cell population, and whether this could be correlated with the stage of the illness. PBMN cells from acute and chronic patients and healthy donors were cultured in presence of RCM-RB51 antigen or phytohemagglutinin as positive controls. After optimal day incubation, 60 micromol BrdU (5-bromo-2-deoxyuridine) was added for the final 6 hours of activation. Cells were harvested, then permeabilized and stained with anti-BrdU-FITC-DNAse and CD3- CD4- or CD8-PE. Data acquisition was performed and analyzed in a cytofluorometer. When cells were challenged with the RCM-RB51 antigen, there was a highly significant (p<0.001) proliferation of both CD4+ and CD8+ T lymphocytes derived from acute and chronic patients, when compared with healthy controls. However, there were not statistical differences when compared acute versus chronic patients. Though the incorporation of BrdU showed similar results, our data suggest an important role for both CD4+ and CD8+ T lymphocytes in Brucella infection in humans. As it has been reported in mice, it is feasible that activated CD8+ T cells participate in protection against Brucella in humans through cytotoxicity and/or by the production of factors such as interferon and granulysin. The role of these cells should be carefully analyzed to better understand their participation in the human infection by Brucella. [ABSTRACT FROM AUTHOR]

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (Treg) cells are still unknown. Our goal was to determine whether PRL plays a role in Treg function. We measured the expression of PRL and its receptor in Treg and effector T (Teff) cells from 15 healthy individuals. We also evaluated the functional activity of Treg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that Treg cells constitutively expressed PRL receptor, whereas Teff cells required stimulation with anti- CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by Treg cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of Treg and Teff cells (P&grt;0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFN&ggr;.We report for the first time that PRL receptor expression was constitutive in Treg cells but not in Teff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of Treg cells, apparently through the induced secretion of Th1 cytokines. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most frequent cancer in women in Mexico, and its development depends on the presence of human papillomaviruses in the uterine cervix. These oncogenic viruses transform cells where the control over cell cycle disappears, and the capacity to induce apoptosis is absent. On the other hand, some mutations confer to the transformed cells the ability to evade recognition by the immune system. The expression of markers of the immune system such as CD95, MICA/B, CD39, CD73, NKp30, NKp46, CD44, CD24, NKG2A, and CTLA-4 was analysed by flow cytometry on cervical cancer cells INBL (HPV 18, stage IVB), HeLa (HPV 18), CaSki (HPV 16), and C33A (HPV-). Our results showed the presence of atypical markers on cervical cancer cells; some of them are molecules involved in tumour cell recognition such as MICA/B and CD95. Other markers associated with immune system escape, such as CD39, CD73, and CTLA-4, were also present. Furthermore, we found that some cervical cancer cells expressed typical markers of NK cells like NKp30, NKp46, NKG2A, and KIR3DL1. It is not clear whether these molecules confer any gain to the tumour cells or if they represent a disadvantage, but we hypothesise that these molecules that are present in cervical cancer cells allow them to mimic in front of the immune system.

CD8 + T cells that secrete proinflammatory cytokines play a central role in exacerbation of inflammation; however, a new subpopulation of CD8 regulatory T cells has recently been characterized. This study analyzes the prominent role of these different subpopulations in the development of graft-versus-host disease (GVHD). Samples from 8 healthy donors mobilized with Filgrastim® (G-CSF) and 18 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated by flow cytometry. Mobilization induced an increase in Tc1 ( p < 0.01), Th1 ( p < 0.001), Tc17 ( p < 0.05), and CD8 + IL-10 + cells ( p < 0.05), showing that G-CSF induces both pro- and anti-inflammatory profiles. Donor-patient correlation revealed a trend ( p = 0.06) toward the development of GVHD in patients who receive a high percentage of Tc1 cells. Patients with acute GVHD (aGVHD), either active or controlled, and patients without GVHD were evaluated; patients with active aGVHD had a higher percentage of Tc1 ( p < 0.01) and Tc17 ( p < 0.05) cells, as opposed to patients without GVHD in whom a higher percentage of CD8 Treg cells ( p < 0.01) was found. These findings indicate that the increase in Tc1 and Tc17 cells is associated with GVHD development, while regulatory CD8 T cells might have a protective role in this disease. These tests can be used to monitor and control GVHD., Competing Interests: The authors declare that they have no competing interests.

Aim: The aim of this paper was to evaluate the effect of a treatment with glycophosphopeptide on Olympic high platform divers during training and competition by measuring lymphocytes and cortisol in peripheral blood, and secretory immunoglobin A in saliva (sIgA)., Methods: Two groups of 8 divers were given a 14-day treatment of capsules (Gp or placebo) three times per day. Measurements of the peripheral blood lymphocytes (TCD3+, TCD4+ and T CD8+), plasma cortisol and IgA levels in saliva were made on day 0, 21 and 150., Results: There was no significant difference found between the Gp- and placebo-treated groups regarding the increase in IgA between basal and first, or first and second measurements. The fact that there was a significant increase in S-IgA (9.89 ± 0.44 to 10.59±0.55, P=0.001) and B CD19+ (345.13±108.24 to 484.75±120.54, P=0.025) in the Gp- and not in the placebo-treated group between the basal and first measurement was due to the variation among the athletes of the latter group, and not the increase itself, indicating that Gp acted as an immunomodulator. It was apparently the exercise and not the Gp treatment that caused the increase in S-IgA and B CD19+ at the first and second measurements., Conclusion: The current study reports that with athletes who practiced moderately intense exercise, which stimulated the immune response, a Gp treatment of two weeks seems to have acted only as an immunomodulator that reduced the variation in the increased levels of IgA and B CD19+.

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still unknown. Our goal was to determine whether PRL plays a role in T(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.

The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jalpha18(-/-) mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using alpha-galactosylceramide (alpha-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d(-/-) mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-gamma but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28:0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-gamma production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to alpha-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess.

In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3(+) cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161(+) T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161(+) T cells; upregulation of CD69 was observed on both CD161(-) and CD161(+) T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN-gamma but no IL-4, IL-5 and IL-13 by CD161(+) T cells in all groups; upon polyclonal stimulation, there were more CD161(+) T cells producing IFN-gamma and less CD161(-) T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161(+) T cells are activated and are able to produce predominantly IFN-gamma but no Th2 cytokines. We hypothesize that during an asthma attack, IFN-gamma produced by CD161(+) T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks.

Brucellosis is still a critical public health problem in many countries around the world. In humans, the infection is mainly acquired through the ingestion of milk-derived products from infected cattle. After the penetration of the bacteria in the body, several serum components are activated, and the immediate consequence is the attraction of phagocytic cells. The evolution of the disease often courses to a long lasting form, with frequent relapses. This appears to be due to the capability of Brucella's of surviving and, even more, multiplying within the mononuclear phagocytic cells. First, the intracellular location protects the bacteria from the effect of antibiotics. On the other hand, several studies have shown alterations in the phagocytic function. In some cases, the defects in phagocytosis are intrinsic to the host. However, Brucella organisms also display many mechanisms to evade the intracellular killing, which appears to be the reason for the success of the bacterium in dwelling within macrophages.

We compared the immunological responses of leukocytes taken from healthy negative controls, laboratory workers immunized with the phenol-insoluble French vaccine against brucellosis, patients acutely ill with brucellosis, and patients chronically infected with Brucella melitensis. A salt-extractable antigen (protein-rich but with traces of lipopolysaccharide) and a sonicated suspension from B. melitensis 16M were used as antigens for in vitro lymphocyte proliferation test. Quantitation of T cells showed that the ratio of CD4+/CD8+ cells decreased as the condition of the patient deteriorated. An assay to quantitate the cell-mediated immunity showed that the activities of mononuclear cells stimulated with concanavalin A increased as the disease progressed as well.