Characteristics of CD4+ and CD8+ Memory T Cell Subsets from Peripheral and Bone Marrow in Patients with Acute Myeloid Leukemia

Abstract

T cell immune surveillance is considered to be an important host protection process to inhibit carcinogenesis. The full capacity of T cell immune surveillance dependent a lot on T cell homeostasis, especially for central memory T (TCM) cells and stem cell memory T cells (TSCM), the latter is a newly identified memory T cell subset. While, the distribution of different memory T cell subsets in patients with leukemia remains unclear. In the present study, we assayed and compared the distribution of CD4+ and CD8+ TSCM, TCM, T effector memory (TEM) and T terminal effector (TEF) cells in peripheral blood (PB) and bone marrow (BM) of patients with acute myeloid leukemia (AML) by multicolor flow cytometry (The gating strategy is shown in figure 1), and 27 PB samples from healthy individuals (HIs) served as control. Firstly, when compared the all of 16 AML PB samples (Median age is 61.5) with 27 HIs (Median age is 62), it was shown that both the proportion of TSCM and TCM subsets in CD4+ and CD8+ T cells displayed a decreased tendency, while the reduction was most significant in CD8+ TSCM (P= 0.038) and TCM (P= 0.043), on the contrary, the proportion of TEM and TEF increased in some degree in AML group, while it was most significant in CD8+ TEM subset (P= 0.031) (Figure 2). As well known that memory T cell subsets distribution could change with ageing, we further divided AML and HIs into two groups (group I with ages younger than 60 years and group II with ages older than 60 years), and compared the T cell subsets distribution in each group, it was interesting that more striking differences were discovered in younger age group, except for CD4+ TSCM, TCM and CD8+ TEF subsets, however, there was no difference in any subsets of old age group (Figure 3). We also compared the percentage of the memory T cell subsets between PB and BM from 7 patients with AML, the difference in each subsets seemed individual, interestingly, we observed an accordant reduction in CD4+TCM and corresponding increase inCD4+ TEM and TEF subsets in BM compared with PB (Figure 4), however, this result is still needed further investigation with a large cohort samples to verify it. Combining our recent findings that higher Tim-3 (T-cell immunoglobulin and mucin-domain containing protein 3) and PD-1 (Programmed death 1) expression and exhausted phenotype (CD244 and CD57) were identified in both CD4+ and CD8+ T cells from patients with AML, it might conclude that no matter young or old AML patient displayed an aging T cell subsets distribution pattern which resembles old healthy individuals, and it might be worse in BM than in PB. For young AML patients, continually virus and tumor antigen stimulation may lead to lower TSCM and TCM and the higher percentage of TEM and TEF, however their higher expression of T cell inhibitory receptors and exhaustion status resulted in the immune escape of AML cells. In terms of old AML patients, both tumor environment and aging destroyed the balance of T cell homeostasis, even there was no more skewed memory T cell subsets distribution pattern detected compared with gerontal healthy individuals, there might have other immune suppressions factors which suppressed T cell function and lead to the poor survival, further research will be needed to figure out this issue. [Display omitted] DisclosuresLi:National Natural Science Foundation of China (91642111): Research Funding; Guangdong Provincial Applied Science and Technology Research & Development Program (No. 2016B020237006): Research Funding; Guangdong Provincial Basic Research Program (No. 2015B020227003: Research Funding; Guangzhou Science and Technology Project (No. 2015100010211): Research Funding.