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

Abstract

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.

Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

“…Several studies have shown that a certain population of phenotypical mature DC, expressing high levels of costimulatory molecules and/or MHC-II molecules, may induce T-cell unresponsiveness and also possess tolerogenic properties (5,30,60). A previous study reported that accessory cells in contact with T. cruzi in vitro became incompetent as APC, being unable to induce a normal T-cell proliferative response (32). Here, we demonstrated that the presence of Tp during LPS pretreatment of DC makes them lose their capacity to induce lymphocyte proliferation, in spite of their upregulated expression levels of CD40, CD80, and CD86.…”

Modulation of B-Cell Proliferative Response by a Soluble Extract ofNippostrongylus brasiliensis

“…Part of this accommodation is the ability to modulate host immune responsiveness (25). Modulation of lymphocyte function has been widely reported among nematodes (2,3,19,21,22,28) and other parasites (6,15,27,36). For example, we have previously shown a dramatic potentiation of antibody responses to third party antigens by treatment with a body fluid extract of Ascaris suum (19).…”

“…Similarly, the nematode Heligmosomoides polygyrus has been reported to contain immunomodulatory factors capable of either stimulating (37,38) The prevailing evidence supports a significant role for accessory cells in the activation of T and B cells both in vivo and in vitro (7, 41). This has prompted numerous investigations into the role of macrophages in helminth-mediated immunomodulation of lymphocyte function (2,15,17,22,27,28,36). These studies have demonstrated a significant role for macrophages in the effects of helminths on developing immune responses.…”

“…Moreover, N. brasiliensis larvae activate alveolar macrophages to produce cytokines postulated to contribute to the robust type 2 immune response associated with nematode infection (12). Other studies have reported parasite factors that either alter accessory cell costimulation or cause accessory cells to produce factors (such as prostaglandins, nitric oxide, hydrogen peroxide, and superoxide anion), which mediate a change in lymphocyte function (2,15,17,27,28,36). These effects of parasites on accessory cell function are likely to have a significant effect on the outcome of infections experienced concurrently.…”

“…This has prompted numerous investigations into the role of macrophages in helminth-mediated immunomodulation of lymphocyte function (2,15,17,22,27,28,36). These studies have demonstrated a significant role for macrophages in the effects of helminths on developing immune responses.…”