Immunosuppression in human acute Chagas disease

Voltarelli, J C; Donadi, Eduardo Antônio; Falcão, Roberto Passetto

doi:10.1016/0035-9203(87)90324-5

Cited by 19 publications

(9 citation statements)

References 6 publications

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“…The acute phase of Chagas' disease in laboratory animals and patients is accompanied by severe alterations of the humoral and cellular arms of the immune system (Clinton et al 1975, Teixeira et al 1978, Kierszenbaum 1981, Voltarelli et al 1987, Tarleton 1988. The suppression of the immune response in this parasitic infection may be regarded as aiding in the establishment of the parasite in the host.…”

Section: Introductionmentioning

confidence: 99%

Involvement of accessory cells in the Trypanosoma cruzi‐induced inhibition of the polyclonal response of T lymphocytes

Motrán

Gruppi

Vullo

et al. 1996

Parasite Immunology

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Infection with Trypanosoma cruzi is characterized by hyporesponsiveness of the immune system during the acute phase of infection. To better understand the immunological mechanisms affected by T. cruzi, we studied if a reduced T cell proliferative response could originate from an inability of T cells to proliferate or a functional deficiency at the level of accessory cells (AC). The inhibitory effect exerted by T. cruzi was during the induction phase of the lymphoproliferative response, suggesting the participation of AC in the hyporesponse. Then we further investigated the potential of the parasite to interfere with accessory cell-dependent and -independent pathways of human T cell proliferation. Peripheral blood mononuclear cells and peripheral blood lymphocytes from healthy individuals, enriched for T cells, were analysed with regard to their proliferative capacity using: phytohaemagglutinin, immobilized anti-CD3 monoclonal antibody (MoAb) and MoAb to the CD28 antigen, anti-CD3 MoAb and recombinant IL-2 and anti-CD3 MoAb plus phorbol myristate acetate in the presence of parasites. Significant suppression of the proliferative response was caused by the parasite only when AC were present. The parasite markedly reduced the surface expression of HLA-DR and CD11b antigens, key molecules in PHA-induced proliferation. Addition of indomethacin to the culture failed to reverse the inhibitory effect of the parasites, suggesting that prostaglandin E2 was not involved. These data suggest that AC in contact with T. cruzi become incompetent as antigen presenting cell because they are unable to induce a normal proliferative response in T lymphocytes.

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Section: Introductionmentioning

confidence: 99%

Involvement of accessory cells in the Trypanosoma cruzi‐induced inhibition of the polyclonal response of T lymphocytes

Motrán

Gruppi

Vullo

et al. 1996

Parasite Immunology

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“…Associated with the inflammatory response in host tissues, an important cellular and humoral immunosuppression in the acute phase of T. cruzi infections has been described (10, 22,28). Therefore, it is possible that nonspecific mechanisms play an important role in protecting the host.…”

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CD8+ cells and natural cytotoxic activity among spleen, blood, and heart lymphocytes during the acute phase of Trypanosoma cruzi infection in rats

et al. 1992

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The infection developed by Wistar Furth rats inoculated with the Y strain of Trypanosoma cruzi was the experimental model used in our study. The results showed that this infection altered considerably the CD4/CD8 lymphocyte subset ratio and the natural cytotoxic activity of mononuclear cells in the spleen, blood, and myocardial tissue. Concomitantly, an expansion of the number of cells expressing major histocompatibility complex (MHC) class II antigens was observed, as well as spontaneous development of high levels of blast cells, mainly in the spleen. The inflammatory infiltration of the myocardium, made up essentially of CD8+ cells (cytotoxic/suppressor T cells, natural killer cells), was initially found at 9 days postinfection, spread continuously, and was observed until the death of the animals at about 18 days postinfection. T. cruzi infection also enhanced the natural killer activity of mononuclear cells in the blood, spleen, and myocardium. Sorting these cells by affinity columns showed that the natural killer function was performed exclusively by the CD8+ population, which did not express MHC class II antigens. It was shown that the polyclonal T-lymphocyte activation induced by T. cruzi infection results in a wide distribution of CD8+ cells with enhanced natural cytotoxic activity in the spleen, blood, and cardiac tissue.

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“…In the mouse model system of Chagas' disease, these effects have been attributed to increased suppressive activities by splenic T cells (22) or macrophages (8,15), reduced levels of T cells (13), and decreased interleukin-2 (IL-2) production (12,26,27). In patients with Chagas' disease, immunosuppression has been reported to occur in the acute and subacute phases, at least in the form of suppressed cellular immunity (28,30). Whereas all of these studies have focused on the immunological alterations that occur in infected hosts, our understanding of the underlying mechanism(s) is minimal.…”

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Selective suppressive effects of Trypanosoma cruzi on activated human lymphocytes

1989

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The acute phase of Chagas' disease is accompanied by immunosuppression. To explore the underlying mechanism(s), we used an in vitro culture system in which the capacities of activated human peripheral blood mononuclear cells to express interleukin-2 receptors (IL-2R) and proliferate are markedly inhibited in the presence of Trypanosoma cruzi, the etiologic agent. The present work was designed to define the earliest time at which T. cruzi-induced suppression is manifested in terms of IL-2R expression on the cell surface and establish whether expression of other lymphocyte activation markers is also suppressed by the parasite. We found that expression of IL-2R by human peripheral blood mononuclear cells cocultured with T. cruzi and stimulated with either phytohemagglutinin or anti-CD3 (a monoclonal antibody specific for an epitope of the T cell receptor complex T3-Ti) was significantly suppressed as early as 12 h after culture initiation. Both the percentage of IL-2R+ cells and the surface density of IL-2R, measured by flow cytometry, were affected. However, expression of EA1, a human lymphocyte activation antigen known to be expressed 4 to 6 h after stimulation, was not altered by T. cruzi whether phytohemagglutinin or anti-CD3 was used. On the other hand, expression of transferrin receptors (TfR), which first occurs between 20 and 24 h after lymphocyte activation, was markedly suppressed by T. cruzi. This effect was denoted by significant reductions in both the percentage of TfR+ cells and the cell surface density of TfR whether phytohemagglutinin or anti-CD3 was used as the mitogen and was observed at all test times, i.e., at 24, 48, 72, and 96 h. Because expression of IL-2R and TfR is required for lymphoproliferation but that of the EAl lymphocyte activation marker is apparently not, these results are consistent with the possibility that T. cruzi, at a relatively early stage during lymphocyte activation, selectively affects certain key events on which clonal expansion is dependent. Inhibition of IL-2R and TfR expression by the parasite might play a role in causing the suppressive effects associated with acute Chagas' disease.

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Immunosuppression in human acute Chagas disease

Cited by 19 publications

References 6 publications

Involvement of accessory cells in the Trypanosoma cruzi‐induced inhibition of the polyclonal response of T lymphocytes

Involvement of accessory cells in the Trypanosoma cruzi‐induced inhibition of the polyclonal response of T lymphocytes

CD8+ cells and natural cytotoxic activity among spleen, blood, and heart lymphocytes during the acute phase of Trypanosoma cruzi infection in rats

Selective suppressive effects of Trypanosoma cruzi on activated human lymphocytes

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