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.

Cellular aging and senescence characteristics of human T-lymphocytes

“…A number of cell surface characteristics has been used to describe senescent T-lymphocytes. These include loss of CD28 expression (Effros 2004), expression of killer cell lectin-like receptor G1 (KLRG1) (Voehringer et al 2002;Ouyang et al 2003), and expression of CD57 (Brenchley et al 2003;Ibegbu et al 2005).…”

The impact of 6-month training preparation for an Ironman triathlon on the proportions of naïve, memory and senescent T cells in resting blood

“…The appearance of KLRG1+ diVerentiated T cells with training could be due to a number of reasons. These include increased incursion of external pathogens due to lowered immune surveillance (Ibegbu et al 2005;Voehringer et al 2001), heightened oxidative stress levels (Reichhold et al 2009b;Turner et al 2011), the release of inXammatory mediators that can impact on T-cell diVerentiation, or to reactivations of latent viruses (Thimme et al 2005;Voehringer et al 2001). Increased levels of oxidative stress in response to arduous endurance training is well established, particularly those that result in lipid peroxidation (Finaud et al 2006).…”

“…Table 3 Phenotypic identiWcation of blood T-cell subsets a Approximately 3-7% of all CD8+ T cells displaying this phenotype may be central-memory T cells (Koch et al 2008) b Although this phenotype identiWes naïve T cells, highly diVerentiated eVector-memory CD8+ T cells can re-express CD45RA without co-expressing CD45RO. These cells can account for around 20% of total CD8+ T cells (Sallusto et al 1999(Sallusto et al , 2004 C The term "senescent" has been used to describe cells with this phenotype, however, some KLRG1+/CD28-cells may be in a state of "exhaustion" and their proliferative capabilities may be restored under certain circumstances (Akbar and Henson 2011) d The variation in CCR7 expression (28-57%) among KLRG1+/CD28+ cells (Ibegbu et al 2005) Akbar et al (1988) 21°C, and average temperatures of 12 and 17°C for the bike and run components were recorded, respectively. Changes in subject physical characteristics in response to the 6-month training period are presented in Table 1.…”

“…The training regimen resulted in an increased proportion of diVerentiated CD8+ T cells expressing KLRG1 (KLRG1+/CD57¡), which are antigen-experienced memory cells that have limited proliferative potential (Ibegbu et al 2005;Voehringer et al 2002). CD8+ T cells expressing KLRG1 are less responsive to mitogens and cognate antigens (Henson et al 2009;Ibegbu et al 2005;Voehringer et al 2002), indicating that an accumulation of KLRG1+ T cells with exercise could lower the naïve antigen T cell repertoire, impairing immune responses to newly evolving pathogens (i.e. inXuenza, rhinovirus, RSV) during periods of heavy training and competition.…”

“…Early diVerentiated T cells retain CD28, but express KLRG1 and the memory cell marker CD45RO (KLRG1+/ CD28+/CD45RA¡/CD45RO+). Following excessive rounds of cell division, memory T cells acquire a senescent phenotype by losing CD28 and expressing CD57 (KLRG1+/ CD28¡/CD57+) (Ibegbu et al 2005). Blood T cells expressing KLRG1 are known to have very little (KLRG1+/ CD28+/CD57¡) or no proliferative capacity (KLRG1+/ CD28¡/CD57+) in response to mitogenic stimulation in vitro (Ibegbu et al 2005;Voehringer et al 2002) and expansion of these cell populations are associated with persistent viral infections and ageing (Ibegbu et al 2005;Ouyang et al 2003).…”