Dynamics of Lymphocyte Populations during Trypanosoma cruzi Infection: From Thymocyte Depletion to Differential Cell Expansion/Contraction in Peripheral Lymphoid Organs

Abstract

The comprehension of the immune responses in infectious diseases is crucial for developing novel therapeutic strategies. Here, we review current findings on the dynamics of lymphocyte subpopulations following experimental acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. In the thymus, although the negative selection process of the T-cell repertoire remains operational, there is a massive thymocyte depletion and abnormal release of immature CD4(+)CD8(+) cells to peripheral lymphoid organs, where they acquire an activated phenotype similar to activated effector or memory T cells. These cells apparently bypassed the negative selection process, and some of them are potentially autoimmune. In infected animals, an atrophy of mesenteric lymph nodes is also observed, in contrast with the lymphocyte expansion in spleen and subcutaneous lymph nodes, illustrating a complex and organ specific dynamics of lymphocyte subpopulations. Accordingly, T- and B-cell activation is seen in subcutaneous lymph nodes and spleen, but not in mesenteric lymph nodes. Lastly, although the function of peripheral CD4(+)CD8(+) T-cell population remains to be defined in vivo, their presence may contribute to the immunopathological events found in both murine and human Chagas disease.

Figure 1

Lymphocyte subsets in central and peripheral lymphoid organs from T. cruzi acutely infected mice. Male BALB/c mice were infected intraperitoneally with 10² culture-derived trypomastigotes of T. cruzi (Tulahuén strain), and 14 days after infection the subcutaneous lymph nodes (SCLN), mesenteric lymph nodes (MLN), peritoneal cavity cells (PC), and spleen were harvested to perform flow cytometry. Erythrocytes were previously depleted in the spleen cell suspensions by treatment with Tris-buffered ammonium chloride. The total number of (a) double-negative CD4⁻CD8⁻ T cells, (b) double-positive CD4⁺CD8⁺ T cells, (c) single-positive CD4⁺ T cells, and (d) CD8⁺ T cells, (e) CD19⁺IgD^low B cells and (f) CD19⁺IgD^high B cells are indicated for each histogram. Values represent the mean and standard error. The infected group (n = 5–14) were compared to noninfected controls (n = 4–9) with t-test, using the program GraphPad Prism 5. Data were considered significant if P values were <0.05. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Distinct pattern of lymphocyte fluctuations in central and peripheral lymphoid organs during acute Trypanosoma cruzi infection. The upper panels depict thymus and peripheral lymphoid sites, in terms of T- and B-cell subsets. It is illustrated the thymic atrophy, simultaneously with an increase in mature and immature export of cells from the organ, as well as hyperplasia of spleen and subcutaneous lymph nodes that course in parallel with an atrophy of the mesenteric lymph nodes, whereas the peritoneal cavity remains rather unchanged (except for the significant rise in CD4⁺ and CD8⁺ T-cell subsets). Bottom panels reveal fold changes of each T- and B-lymphocyte subsets from acutely infected mice over the corresponding controls.