Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)

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Abstract
Adaptive immunity necessitates the proliferation of lymphocytes. In the mouse, we have previously shown that antigen-experienced T cells that have lost their proliferative potential express the killer cell lectinlike receptor G1 (KLRG1). By using a newly generated monoclonal antibody specific for human KLRG1, we now demonstrate that expression of KLRG1 also identifies T cells in humans that are capable of secreting cytokines but that fail to proliferate after stimulation. Furthermore, our data show that proliferative incapacity of CD8 T cells correlates better with KLRG1 expression than with absence of the CD28 marker. In peripheral blood lymphocytes (PBLs) from healthy adult donors, KLRG1 was expressed on 44% ± 14% of CD8 and 18% ± 10% of CD4 T cells. KLRG1 expression was restricted to antigen-experienced T cells. Here, KLRG1+ cells were preferentially found in the CCR7− effector T-cell pool. Besides T cells, a significant portion (approximately 50%) of human natural killer (NK) cells expressed KLRG1. Interestingly, these KLRG1+ NK cells were found exclusively in the CD56dim NK-cell subset. Thus, the expression of KLRG1 identifies a subset of NK cells and antigen-experienced T cells in humans that lack proliferative capacity.