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Deregulations of T and B lymphocyte responses

Defective lymphocyte responses

Immunosuppression has been broadly documented in T. cruzi-infected humans. It results from both direct and indirect action of parasites on lymphocytes. Mechanisms are detailed by Truyens and Carlier.3 Briefly, suboptimal B and T lymphoproliferative responses result from insufficient activation of Ag presenting cells and perturbations of the IL-2/IL-2R pathway. Myeloid-derived suppressor cells (MDSC)174,175 and PGE283 also contribute to immunosuppression. MDSC may however also exert a beneficial role by preventing excessive inflammation.176 The recently disclosed interaction of the parasite cruzipain with the inhibitory receptor

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Siglec-E might also contribute to dampen the immune response.

Besides, apoptosis of B and T lymphocytes, particularly pronounced during the acute phase of infection, likely contributes to delay the Ab response. B and T cell depletion depends on Fas/FasL, TNF-a, and NO pathways, as well as the action of the parasite trans-sialidase.3,181 Apoptosis of CD41 T cells, but not of CD81 T cells, in chronic infection is rather related to the physiological process of activation-induced programmed cell death.182

Finally, suboptimal specific response also relates to the abundant expression by T. cruzi of polymorphic molecules of the TS superfamily. Some T cell epitopes of these molecules are major CD41 T cell antigens (the variant SA85-1.1, for instance) and have a low affinity for T cell TCRs. They therefore induce incomplete or anergic T cell rather than optimal responses.183 Such “altered peptide presentation” may have a substantial impact in biasing the global response to suboptimal (though Th1) levels.103

 
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