Modification of T-cell proliferation and interleukin 2 production in mice infected with Trypanosoma cruzi.

Abstract

Acute infection of mice with Trypanosoma cruzi results in severe immunodepression and the appearance of autoimmune symptoms. In vitro, concanavalin A-stimulated T cells from spleens of infected animals could neither produce nor respond to interleukin 2. Interleukin 2 production was not restored by addition of exogenous interleukin 1, and proliferative response to concanavalin A was not restored by exogenous interleukin 2. A population of Thy-i-negative cells in the spleen of infected animals was shown to suppress the concanavalin A proliferative response and, to a lesser extent, the production of interteukin 2. These and other symptoms of T. cruzi-infected mice are similar to the immune dysfunction of autoimmune Ipr/lpr mice. These findings are discussed in relationship to the pathology of Chagas disease.Trypanosoma cruzi causes Chagas disease in man. The disease is characterized by a variable acute phase during which trypomastigotes circulate, followed by a lifelong chronic phase in which parasites are not detected in circulation but rather appear to be sequestered in the tissues (1). The parasites persist in the chronically infected individuals in spite of the presence of high levels of circulating anti-T. cruzi antibodies. The mouse has been used as a laboratory model for Chagas disease because injection of parasites gives rise to both acute and chronic infections.Severe perturbations of the host immune system accompany T. cruzi infections in the mouse (1-4). On one hand, autoantibodies directed to various host antigens are induced. On the other hand, severe immunodepression has been reported to occur during the acute phase of the infection, and cellular responses to mitogens, parasite antigens, or irrelevant antigens are depressed. These results suggest that the parasites perturb the host immune system at the level of the T cells. We have studied this possibility by examining T-cell proliferation and the production of T-cell regulatory molecules in T. cruzi-infected mice.Interleukin 2 (IL-2) appears to play a key role in the regulation of cellular immune responses (5, 6). It is produced by T lymphocytes in the presence of interleukin 1 (IL-1) and mitogen or antigen, and it sustains the proliferation of helper and effector T lymphocytes and thus amplifies the effector phase of the immune response. Because of this central role of IL-2 in regulating the immune response, we have examined its production and activity in T. cruzi-infected mice.We report here that acute infection with T. cruzi results in a severe depression of IL-2 production which parallels the depressed proliferative response to the mitogen concanavalin A (Con A). Furthermore, Thy-l-spleen cells from infected animals are able to suppress the proliferative response to Con A and, to a lesser extent, IL-2 production by spleen cells from normal animals. MATERIALS AND METHODSMice and Infection. All experiments were performed with pools of three to eight C3H/HeJ Pas male mice (Pasteur Institute, Paris). Mice were 6-8 weeks of age at the time of...

Differentiation of entamoeba histolytica/entamoeba dispar by PCR and their correlation with humoral and cellular immunity in individuals with clinical variants of amoebiasis.

“…Suppression of the cellular immune response has been observed during the infection by protozoan parasites, including Leishmania donovani 56 and Trypanosoma cruzi. 23 There is also evidence that the response of T cells is systematically suppressed during the acute illness due to E. histolytica, as has been observed in animal models 57 and in patients with amoebic hepatic abscess. 49 Serum from E histolytica-infected gerbils 58 and immune sera from patients 25 selectively suppress T cell proliferation by inhibiting IL-2 and IFN-␥ production.…”

“…49 Serum from E histolytica-infected gerbils 58 and immune sera from patients 25 selectively suppress T cell proliferation by inhibiting IL-2 and IFN-␥ production. Previous studies have shown that in infections caused by pathogens that induce immunosuppression in the host, such as L. donovani, 56 HIV, 59 and T. cruzi, 23 the outcome of the relationship could be regulated by CD4+ helper T cells with different pattern of cytokines. Protective immunity would be associated with Th1 cells that produce INF-␥ and IL-2, whereas Th2 cells, which produce immunosuppressive IL-4 and IL-10, could facilitate the survival and dissemination of the parasite generating tissue damage and the appearance of the disease.…”

“…in animal models, 21 and the data has been confirmed with other pathogenic agents. [22][23][24] During invasive amoebiasis, decrease of CD4+ cells, increase of CD8+ cells, as well as decrease in in vitro proliferation of T lymphocytes against amoebic antigens have been described. 25 Also an immunosupressive state has been observed on delayed cutaneous hypersensitivity against amoebic antigens.…”

Study of the Biological Activities of Toxic Shock Syndrome Toxin‐1

“…Actually we found that macrophage activating factor (MAF) is produced by TSST-1-stimulated T cells (unpublished data). It has been thought that lymphokines are essential in the regulation of the immune response (12) and the acquisition of resistance to microbial infections (13,14). In hosts infected with TSST-1-producing staphylococci, however, lymphokines including IL 2 are presumed to be produced in excess over the physiologically required amounts; substantial amounts of IL 2 and MAF were produced when HPBL were stimulated with 0.1-1 ng of TSST-1 per ml for 12-24 hr (manuscript in preparation).…”

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

“…The acute phase of Chagas' disease in mice is associated with a T cell defect characterized by a decreased production of IL-2 in response to parasite antigens and T cell mitogens [1][2][3]. In contrast, production of interferon-gamma (IFN-) during the second week of infection is increased, as indicated by accumulation of IFN-mRNA in spleen and increased in vitro secretion of IFN-by spleen cells [4].…”