Bone marrow T cells populations are differently affected by sepsis than their splenic counterparts in the murine sepsis cecal ligation and puncture (CLP) model

Abstract

Abstract Sepsis is known to induce lymphopenia which correlates with secondary infections and mortality. In sepsis survivors the lymphocyte count restores with time, although the T cell responses are impaired. So far, the mechanisms of T cells recovery are not fully understood and the murine studies were focused on the peripheral lymphatic organs in which the spleen was most common. Our study was designed to elucidate the recovery of bone marrow (BM) T cells which contain population of memory cells, after the CLP murine sepsis. In our model, mild CLP produced peripheral lymphopenia which was lowest at 48h after CLP but after 7 days circulating T cells count was rebounding. 7 days after CLP the BM frequencies of naïve and central memory (CD44+CD62L+) CD4 cells were unchanged while they were reduced in the spleen. Percentage of effector memory (CD44+CD62L−) CD4 and CD8 cells increased in the BM and at the same time they dramatically decreased in the spleen. On the contrary, the effector (CD44−CD62L+) CD4 and CD8 cells expanded at that time point in the spleen while they did not change in the BM. At D7 after CLP, the rates of BrdU+ proliferating CD4+ and CD8+ cells were markedly higher in the BM than spleen. Among the BM CD4+ cells most of the proliferating cells were the effector memory cells, while the effector CD4+ had highest proliferation rate in the spleen. Similarly, CD8 effector memory cells in the BM and CD8 effector cells were most extensively proliferating in the BM and the spleen, respectively. Taken together, our data point to the BM as the place of effector memory T cell proliferation during post-sepsis recovery.