The Development of Unconventional Extrathymic Activated CD4 + CD8 + T Cells in Chagas Disease

Abstract

The numbers of extrathymic CD4 + CD8 + double-positive (DP) T cells are augmented in various pathophysiological conditions, such as infectious diseases caused by intracellular pathogens, organs subjected to autoimmune attack and malignant tumors. The roles performed by extrathymic DP T cells are not clear, and it is not known how they are distributed in the body. In animals they have been considered memory cells involved in adaptive immune responses against virus infections or participating in pathological responses. In experimental Trypanosoma cruzi infections, there is a severe thymic atrophy and this results in the release of activated DP T cells to peripheral organs. In severe cardiac forms of human chronic Chagas disease activated HLA-DR + DP T cells are present in the blood. In investigating the basis of premature thymocyte release during chagasic thymic atrophy we found that the parasite trans -sialidase (TS) altered intrathymic thymocyte maturation and was associated with increased numbers of recent T cells in peripheral lymphoid organs. In what follows we propose to describe what is known about the origin of the extrathymic DP T cells in human Chagas disease and animal models of the disease.