Abstract P3058: Myocardial Infarction Impairs T Lymphopoiesis In Mice

Abstract

T lymphocytes, especially CD4 + T cells, play beneficial roles in regulating cardiac repair after acute myocardial infarction (MI). Some patients with MI show lymphopenia, a reduction in blood lymphocyte count. More importantly, lymphopenia negatively correlates with patient outcome. We have previously shown that circulating lymphocyte trafficking to the bone marrow contributes to lymphopenia post-MI. However, whether MI affects T cell production remains uninvestigated. The aim of this study was to investigate whether MI impairs T lymphopoiesis, the process of T cell development. Three to six months old male C57BL/6J mice underwent MI surgery by permanent ligation of the left anterior descending coronary artery. Sham controls were subject to the same procedure with the exception of artery ligation. At 7 days post-MI, we quantified thymic mass, cellularity, developmental thymocytes, and hematopoietic stem/progenitor cells in the bone marrow and thymus using multiparameter flow cytometry. Thymocyte apoptosis was evaluated using an Annexin V assay kit. Compared to sham controls, MI mice at day 7 post-MI exhibited smaller thymus, lower cellularity, and less thymocytes at different developmental stages, including double negative CD4 - CD8 - , double positive CD4 + CD8 + , and single positive CD4 + thymocytes. Early thymic progenitors (ETP) that generate thymocytes in the thymus were also lower in MI mice than sham counterparts. Interestingly, common lymphoid progenitors (CLP) in the bone marrow, the ancestors of ETP, were not affected by MI. To determine the reason that MI mice show less thymocytes, we assessed thymocyte apoptosis. The data showed that thymocytes in MI mice exhibited higher apoptotic rate than sham controls. In conclusion, our study, for the first time, demonstrates that MI impairs T lymphopoiesis, and this impairment mainly occurs in the thymus, but not in the bone marrow. The underlying mechanisms are related to increased thymocyte apoptosis.