Abstract
Thymic atrophy occurs during infection being associated with apoptosis of double positive (DP) and premature exit of DP and double negative (DN) thymocytes. We observed for the first time that a significant bone marrow aplasia and a decrease in common lymphoid progenitors (CLPs) preceded thymic alterations in mice infected with Trypanosoma cruzi. In addition, depletion of the DN2 stage was previous to the DN1, indicating an alteration in the differentiation from DN1 to DN2 thymocytes. Interestingly, infected mice deficient in IL-6 expression showed higher numbers of DP and CD4+ thymocytes than wild type infected mice, while presenting similar percentages of DN1 thymocytes. Moreover, the drop in late differentiation stages of DN thymocytes was partially abrogated in comparison with wild type littermates. Thus, our results suggest that thymic atrophy involves a drop in CLPs production in bone marrow and IL-6-dependent and independent mechanisms that inhibits the differentiation of DN thymocytes.
Highlights
Thymic involution and decreased thymopoiesis are highly related simultaneous events
lineage negative (Linneg) Sca-1neg c-Kitmed corresponding to common lymphocyte precursors (CLPs) analysis showed that cell percentages in bone marrow of infected mice did not significantly change respect non-infected mice (Supplemental Figure 1A)
These results suggest that bone marrow aplasia and common lymphoid progenitors (CLPs) low numbers can contribute to thymic atrophy
Summary
Thymic involution and decreased thymopoiesis are highly related simultaneous events. During this process the size and function of the thymus is drastically reduced (up to 95%) which can be triggered by several processes such as aging [1], pregnancy [2] or stress [3]. The maturing T cells (thymocytes) can be classified (according to CD4 and CD8 markers expression) in the following major stages: about 5% are double negative (DN) thymocytes, 80% are double positive (DP) thymocytes, 10% are CD4 single positive (SP) and 5% are CD8 SP [6]. DN thymocytes can be subdivided in 4 stages (from DN1 to DN4) characterized by differential expression of CD25 and CD44 markers
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