The Virus-Specific and Allospecific Cytotoxic T-Lymphocyte Response to Lymphocytic Choriomeningitis Virus Is Modified in a Subpopulation of CD8<sup>+</sup>T Cells Coexpressing the Inhibitory Major Histocompatibility Complex Class I Receptor Ly49G2

153

NK cells express several families of receptors that play central roles in target cell recognition. These NK cell receptors are also expressed by certain memory phenotype CD8+ T cells, and in some cases are up-regulated in T cells responding to viral infection. To determine how the profile of NK receptor expression changes in murine CD8+ T cells as they respond to intracellular pathogens, we used class I tetramer reagents to directly examine Ag-specific T cells during lymphocytic choriomeningitis virus and Listeria monocytogenes infections. We found that the majority of pathogen-specific CD8+ T cells initiated expression of the inhibitory CD94/NKG2A heterodimer, the KLRG1 receptor, and a novel murine NK cell marker (10D7); conversely, very few Ag-specific T cells expressed Ly49 family members. The up-regulation of these receptors was independent of IL-15 and persisted long after clearance of the pathogen. The expression of CD94/NKG2A was rapidly initiated in naive CD8+ T cells responding to peptide Ags in vitro and on many of the naive T cells that proliferate when transferred into lymphopenic (Rag-1−/−) hosts. Thus, CD94/NKG2A expression is a common consequence of CD8+ T cell activation. Binding of the CD94/NKG2A receptor by its ligand (Qa-1b) did not significantly inhibit CD8+ T cell effector functions. However, expression of CD94 and NKG2A transgenes partially inhibited early events of T cell activation. These subtle effects suggest that CD94/NKG2A-mediated inhibition of T cells may be limited to particular circumstances or may synergize with other receptors that are similarly up-regulated.

mentioning

confidence: 81%

Viral and Bacterial Infections Induce Expression of Multiple NK Cell Receptors in Responding CD8+ T Cells

McMahon

Zajac

Jamieson

et al. 2002

153

“…Previous studies showed that LCMV-and influenza-specific CD8 ϩ T cell populations express Ly49A or Ly49G2 NK receptors, respectively (2,36). To determine whether LCMV-specific CD8 ϩ T cells express Ly49 receptors, we stained splenocytes with mAbs specific for Ly49 A, D, F, G2, I/C, and I receptor isoforms at multiple time points following acute LCMV infection.…”

Section: Resultsmentioning

confidence: 99%

CD94/NKG2 Expression Does Not Inhibit Cytotoxic Function of Lymphocytic Choriomeningitis Virus-Specific CD8+ T Cells

Miller

Peters

Oran

et al. 2002

Murine Ag-specific CD8+ T cells express various NK markers and NK inhibitory receptors that have been proposed to modulate immune responses. Following acute infection of C57BL/6 and BALB/cJ mice with lymphocytic choriomeningitis virus (LCMV), we observed that Ag-specific CD8+ T cells expressed CD94/NKG2. Only slight expression of Ly49A and Ly49C receptors was observed on NP396-specific T cells, while all NP396-specific T cells expressed the NKT cell marker U5A2-13 Ag. Expression of CD94/NKG2 was maintained for at least 1 year following LCMV infection, as was the NKT cell marker. By means of cell sorting and quantitative PCR, we found that NP118-specific CD8+ T cells primarily express transcripts for inhibitory NKG2 receptor isoforms. CD94/NKG2 expression was also observed on Ag-specific CD8+ T cells following infection with polyoma virus, influenza virus, and Listeria monocytogenes, suggesting that it may be a common characteristic of Ag-specific CD8+ T cells following infection with viral or bacterial pathogens. Expression of CD94/NKG2 on memory-specific CD8+ T cells did not change following secondary challenge with LCMV clone 13 and did not inhibit viral clearance. Furthermore, we found no evidence that CD94/NKG2 inhibits either the lytic function of LCMV-specific T cells or their capacity to produce effector cytokines upon peptide stimulation. Finally, down-regulation of CD94/NKG2 was found to occur only during chronic LCMV infection. Altogether, this study suggests that CD94/NKG2 expression is not necessarily correlated with inhibition of T cell function.

“…It might be expected that KLRG1 expression would be lower on Ag-specific cells in the acute, compared with the latent stage. Indeed, there is some evidence that other NK cell inhibitory receptors are not expressed by a large fraction of activated effector CD8 ϩ T cells during acute primary infection with EBV or hepatitis B in humans (20) or lymphocytic choriomeningitis virus in mice (21). It is interesting to add that a recent report has identified preserved or increased expression of inhibitory receptors on NK cells of HIV-infected viremic individuals, in contrast to activating receptors, which were down-regulated in these patients (22).…”

Section: Discussionmentioning

confidence: 99%

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

Ibegbu

Xu²,

Harris³

et al. 2005

159

115

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.