CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells.
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.
Miller
Joseph D
JD
Emory Vaccine Research Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30329, USA.
Peters
Michael
M
Oran
Alp E
AE
Beresford
Guy W
GW
Harrington
Laurie
L
Boss
Jeremy M
JM
Altman
John D
JD
D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000096:biosynthesis* / Q000502:physiology; D000950:Antigens, Ly; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A; D051920:NK Cell Lectin-Like Receptor Subfamily D; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
D015703:Antigens, CD; D000950:Antigens, Ly; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C527088:Klra1 protein, mouse; C527091:Klra3 protein, mouse; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D051920:NK Cell Lectin-Like Receptor Subfamily D; D020033:Protein Isoforms; C032907:Q surface antigens; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell