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In the neonates born to T. cruzi infected mothers, the diagnosis of the congenital transmission relays on the detection of the parasites and/or the specific antibodies non-transferred by their mothers, in the absence of blood transfusion and vectorial transmission. In the early stage, approximately until the 7th month of life, when maternal immunoglobulins could be present, the diagnosis depends on the detection of the parasite. Then, in the late stage, from the 8th month, the detection of specific antibodies by at least 2 of 3 serological tests confirms the infection in the neonates. The diagnostic follow up of the children born to a group of sero-reactive pregnant women was carried out in the INP. The 11% of the mothers (29 out of 267) transmitted the infection to their children. The neonates of 20 of these mothers were diagnosed in the early stage, 14 and 6 in one or two controls, respectively. In the 9 remaining mothers the children were diagnosed in the late stage of the infection, mainly serologicaly. Our analisis of previously published reports stressed that the maternal-fetal transmission rate depends on the time of diagnostic follow up of the child. In this reports, mean values of mother to child transmission reported was 2% and 9% when the diagnosis of the neonates born to sero-reactive mothers was carried out only in the early stage or in the early and also the late stage, respectively.

The outcome of the kidney allograft mainly depends on the immune response and on its complex regulation, where the cytokine network and other mediators play an important role. At present, kidney biopsy is the most useful tool for monitoring the transplant rejection and the diagnosis of the associated nephropathies, in spite of the invasiveness of the procedure. Thus, it is of great interest to find alternative tools for diagnosis. The evaluation of regulatory cytokines is a simple procedure of low cost that could be useful to increase the sensitivity of the detection of polymorphic differences, to predict the graft acceptance and for the early detection of rejection. Recent studies suggest that the high production of pro-inflammatory mediators, such as Th1 cytokines, could be detrimental, whereas the production of anti-inflammatory regulatory cytokines, such as interleukin (IL)-10 and tumor necrosis factor (TGF)-beta, could be beneficial for graft survival. In the early stages, the cellular cytotoxicity is activated by the Th1 response and the detection of cytotoxic molecules is associated to the acute rejection. Later, the balance between pro and anti-inflammatory mediators and the regulation of their levels could be more important. In this regard, TGF-beta is also fibrogenic and a high local production can contribute to kidney damage. On the other hand, the increased production of IL-10 in response to the allogeneic stimuli could be, in most cases, an important marker of long-term acceptance.

Specific antibodies and the activation of phagocytic cells by IFN-gamma are the key elements of the immune response involved in protection of the T. cruzi infected host. The central role of the IFN-gamma in vivo seems to be the activation of the inducible nitric oxide synthetase of macrophages (iNOS) and the production of nitric oxide (NO degree) for the intracellular destruction of the parasite. Interleukin 12 (IL-12), the cytokine that stimulates NK cells for IFN-gamma production, seems to trigger the TH1 response in the acute phase. Other cell types, such as lymphocytes Thy-1+CD4-CD8-, CD4+ and CD8+, are also involved in IFN-gamma production. The down regulation of the TH1 response could in part depend on the decrease in the macrophage activation, as a result of the controlled parasite burden, and on the production of IL-10 and transforming growth factor beta (TGF-beta). The protective TH1 immune response seems to be also related to both the tissue damage and the alterations of the immune response observed during the infection. We studied the kinetics of both NK cell activity, and the production of IL-12 and/IFN-gamma by spleen cells, as well as the seric levels of these cytokines, in BALB/c and C3H mice infected with T. cruzi, Tulahuén strain. In the spleen, we found that the production of IL-12 and the NK cell activity increased in the very early acute infection, and that in C3H the effect was higher than in BALB/c mice. IFN-gamma increased in C3H at the same time, but in the BALB/c strain it increased later in the acute phase. The infection induced a very early increase in the seric levels of IL-12, that remained high throughout the acute phase, in both mouse strains. However, the levels of IFN-gamma in the serum increased a few days before the peak of parasitemia, reaching higher values, and earlier, in BALB/c than in C3H mice. Surprisingly, in the chronic infection IL-12 production remained high in both mouse strains, but IFN-gamma production was only observed in BALB/c mice. The immune response was predominantly TH1 in both mouse strains, in spite of the higher susceptibility of BALB/c compared to C3H. The early control of the parasite burden could be evaluated as the expression of the TH1 response in spleen cells, while the seric levels of IL-12 and IFN-gamma would be related to the induction of tissue damage. Our data indicate that the protective TH1 immune response has a different expression according to the host-parasite relationship, and that the factors controlling the response are of primary importance to determine the quali- and quantitative expression of IL-12/NK/IFN-gamma as well as their involvement in resistance and tissue damage.

The discovery of the superantigens (SAgs) offered new insights on the interaction between microorganisms and the host immune system. Associated to Major Histocompatibility Complex (MHC) class II molecules, SAgs bind to the variable domain of the beta chain (V beta) of the TCR alpha beta engaged in the family specificity of lymphocytes. Therefore, these molecules are able to activate a high number of T lymphocytes as well as surface MHC class II bearing cells, leading to an overriding release of cytokines and inflammatory mediators, which have been related to their toxic effects. Endogenous SAgs are encoded by murine tumor proviruses (Mtv) which are integrated in the genome of mice. Bacteria and viruses produce exogenous SAgs and those related to food poisoning have been widely studied. The presence of parasite SAgs is still unclear and further studies are required to establish their existence and effects on the corresponding infections.

The acute stage of Trypanosoma cruzi infections related to high parasitemia is characterized by the presence of inflammatory infiltrates in several tissues, including the heart and squeletal muscle, as well as by an increased production of inflammatory mediators, such as gamma-interferon (IFN-gamma), tumor necrosis factor (TNF), interleukin-1 (IL-1) and oxygen and nitrogen reactive intermediates. The activation of phagocytic cells seems to be closely related to both the inflammatory process and host resistance to the infection. Herein, the inflammatory mediators produced in vivo and their relationship with the tissue damage and TH1 immune response are reviewed.

Subcellular fractions of T. cruzi epimastigotes (Epi) were studied for their capability to induce protective or aggressive effects in animals. The flagellar fraction (F) showed the best immunoprotective properties without tissular aggression. Monoclonal antibodies were raised against F. Two of them, FCH-F8-1 and 4, were able to neutralize the infectivity of bloodstream forms, to mediate lysis by complement of cell culture derived[trypomastigotes (Tripo) and to recognize the surface of Tripo and Epi. FCH-F8-1 reacted with a 85 kDa protein from Tripo (assayed by immunoprecipitation) and with peptides of 43 kDa on Epi and Tripo (tested by immunoblotting). FCH-F8-4 recognized several proteins ranging from 50 to 150 kDa on Epi and two molecules of 15 and 48 kDa on Tripo. Mice immunized with antigens purified by affinity chromatography by using FCH-F8-4 were protected against the infection. Several recombinant clones were detected on a cDNA lambda gt11 expression library constructed from T. cruzi Epi (Tulahuén strain): three with FCH-F8-4 and two with FCH-F8-1. One clone recognized by each monoclonal antibody was studied gamma (FCH-F8-1) 1 and gamma (FCH-F8-4) 1. Both inserts were of 150 base pairs each; they detected a 3.5 and 5.0 kilobases Epi mRNA, respectively. Both inserts were sequenced, and the amino acid sequences were inferred. gamma (FCH-F8-4) 1 codified for a 19 aa peptide, PAFLGCSSRFSGSFSGVEP, and gamma (FCH-F8-1) 1 for a 29 aa peptide EFLERGRISCORHSYTSYTSCSDEHNVTPFC. The whole 19 aa peptide was synthesized. This peptide (SP4) inhibited the ELISA reactivity against the parasite of chronically infected and F immunized mouse sera.(ABSTRACT TRUNCATED AT 250 WORDS)