CD4(+)CD8(dim) T lymphocytes exhibit enhanced cytokine expression, proliferation and cytotoxic activity in response to HCMV and HIV-1 antigens.
CD4(+)CD8(dim) T cells represent a minor subset of the total CD3(+) T cell population in peripheral blood. Although transient and persistent expansions of these cells have been reported in both healthy and diseased individuals, the functional properties of the CD4(+)CD8(dim) population are largely unknown. In this study, we examined antigen-specific cytokine and proliferative responses of the CD4(+)CD8(dim) subset. In whole blood cultures stimulated with the viral antigens HCMV and HIV-1, a significant fraction of the CD4(+)CD8(dim) subset exhibited cytokine expression and proliferation in response to antigen activation. Typically, the CD4(+)CD8(dim) population contained two- to eightfold higher frequencies of antigen-specific cytokine producing cells than the CD4(+)CD8(-) population. Phenotypic analysis of the cytokine expressing CD4(+)CD8(dim) population indicated that these cells are memory T cells, with a high frequency of this population expressing the cytotoxic markers CD56 and perforin. Furthermore, the CD4(+)CD8(dim) cytokine responses to CMV were shown to be MHC class II dependent. Significantly, purified CD4(+)CD8(dim) T cells were found to possess higher CMV-specific cytotoxic activity than purified CD4(+)CD8(-) T cells in a standard (51)Cr-release CTL assay. Thus, CD4(+)CD8(dim) T cells appear to be MHC class II dependent, are capable of cytolytic effector activity, and are highly enriched within the CD4(+) cell populations specific for HCMV and HIV-1.
Suni
M A
MA
BD Biosciences, Immunocytometry Systems, San Jose, CA 95131, USA. maria_suni@bdis.com
Ghanekar
S A
SA
Houck
D W
DW
Maecker
H T
HT
Wormsley
S B
SB
Picker
L J
LJ
Moss
R B
RB
Maino
V C
VC
D000328:Adult; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma