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. 1992 Oct;77(2):277–283.

Suppression by Trypanosoma cruzi of T-cell receptor expression by activated human lymphocytes.

M B Sztein 1, F Kierszenbaum 1
PMCID: PMC1421637  PMID: 1427979

Abstract

The immunosuppression that develops during Chagas' disease and African sleeping sickness is thought to facilitate survival of the causative agents in their mammalian hosts. Whereas a number of manifestations of immunosuppression manifested during the course of these diseases has been reported in patients and animals, the mechanisms by which they are induced remain obscure. An in vitro system in which phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBMC) were co-cultured with purified Trypanosoma cruzi or T. brucei rhodesiense was used in the present work to establish whether these organisms were able to alter the capacity of activated helper/inducer (CD4+) or cytotoxic/suppressor (CD8+) cells to express T-cell receptor (TcR). Suppressed interleukin-2 receptor (IL-2R), known to be caused by both the trypanosomes and supernatants containing their secretion products, was the independent parameter used to demonstrate the occurrence of immunosuppression in all experiments. We found marked reductions in the percentage of TcR+ cells in T. cruzi-containing cultures as early as 18 hr after PHA stimulation. This alteration was still readily demonstrable after 72 hr of culture, i.e. when last tested for. Suppressed TcR expression occurred concomitantly with reduced levels of CD4 or CD8 molecules on the surface of helper/inducer and cytotoxic/suppressor T lymphocytes, respectively, indicating that the parasite had induced more than one alteration in the same cells. These effects were reproduced when the trypanosomes were separated from the PBMC by a 0.45 micron pore size filter or when filtrates from T. cruzi suspensions substituted for the parasite in the cultures, indicating that TcR suppression was mediated by a parasite secretion product(s). Interestingly, neither T. b. rhodesiense nor filtrates of suspensions of this organism altered significantly the level of TcR expression in cultures in which suppressed IL-2R expression by activated human T cells took place. Thus despite sharing the ability to impair IL-2R expression, T. cruzi and T.b. rhodesiense appear to differ in other mechanisms by which they affect human T-cell function. If occurring in infected hosts, the alterations that T. cruzi causes in the expression of TcR, CD4, CD8 and IL-2R--all molecules playing important roles in lymphocyte activation--could contribute to the development of the immunosuppression observed during the acute phase of Chagas' disease.

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Selected References

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