Virus-specific cytotoxic T lymphocytes differentially express cell-surface leukocyte immunoglobulin-like receptor-1, an inhibitory receptor for class I major histocompatibility complex molecules.
Leukocyte immunoglobulin-like receptor-1 (LIR-1) is an inhibitory receptor that negatively regulates T cell effector functions after interaction with host class I major histocompatibility complex molecules and, additionally, binds to UL18, a human cytomegalovirus (HCMV)-encoded class I homologue. Here, we demonstrate that virus-specific cytotoxic T lymphocytes (CTLs) differentially express LIR-1, with high frequencies of expression on HCMV-specific CD8+ T cells and intermediate and low frequencies of expression on influenza virus-specific and Epstein-Barr virus (EBV)-specific CTLs, respectively. Expression of LIR-1 was dependent on CTL-antigen specificity and was associated with a differentiated effector memory phenotype, as demonstrated by decreased expression of CD28 and increased expression of CD57. During primary HCMV and EBV infections, expression of LIR-1 on virus-specific CTLs was low and increased slowly. These results indicate that expression of LIR-1 increases during differentiation of virus-specific CD8+ effector T cells. Furthermore, they suggest that a potential immunoregulatory function of UL18 may be to preferentially target highly differentiated HCMV-specific effector memory T cells during persistent infection.
Antrobus
Richard D
RD
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom.
Khan
Naeem
N
Hislop
Andrew D
AD
Montamat-Sicotte
Damien
D
Garner
Lee I
LI
Rickinson
Alan B
AB
Moss
Paul A H
PA
Willcox
Benjamin E
BE
D015703:Antigens, CD / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007251:Influenza, Human / Q000276:immunology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic / Q000378:metabolism*; D012008:Recurrence; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D015703:Antigens, CD; D006680:HLA Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic