Expression of Killer Cell Lectin-Like Receptor G1 on Antigen-Specific Human CD8+ T Lymphocytes during Active, Latent, and Resolved Infection and its Relation with CD57

Abstract

Killer cell lectin-like receptor G1 (KLRG1) is one of several inhibitory killer cell lectin-like receptors expressed by NK cells and T lymphocytes, mainly CD8+ effector/memory cells that can secrete cytokines but have poor proliferative capacity. Using multiparameter flow cytometry, we studied KLRG1 expression on CD8+ T cells specific for epitopes of CMV, EBV, influenza, and HIV. Over 92% of CD8+ cells specific for CMV or EBV expressed KLRG1 during the latent stage of these chronic infections. CD8+ T cell cells specific for HIV epitopes were mostly (72–89%) KLRG1+, even though not quite at the level of predominance noted with CMV or EBV. Lower frequency of KLRG1 expression was observed among CD8+ cells specific for influenza (40–73%), a resolved infection without a latent stage. We further observed that CD8+ cells expressing CD57, a marker of replicative senescence, also expressed KLRG1; however, a population of CD57−KLRG1+ cells was also identified. This population may represent a “memory” phenotype, because they also expressed CD27, CD28, CCR7, and CD127. In contrast, CD57+KLRG1+ cells did not express CD27, CD28, and CCR7, and expressed CD127 at a much lower frequency, indicating that they represent effector cells that are truly terminally differentiated. The combination of KLRG1 and CD57 expression might thus aid in refining functional characterization of CD8+ T cell subsets.