Potent HIV-specific responses are enriched in a unique subset of CD8+ T cells that coexpresses CD4 on its surface.
In humans, approximately 3% of peripheral CD8+ T cells coexpress CD4 dimly on their surface and hence are designated as CD4(dim)CD8(bright) T cells. We evaluated the contribution of this CD4(dim)CD8(bright) T-cell population to anti-HIV immunity. We demonstrate that CD4(dim)CD8(bright) T cells generate greater than 55% of CD8+ T-cell antigen recognition and effector response to HIV, as evaluated by multiple parameters for assessing T-cell antiviral immunity, including HIV tetramer recognition, cytokine production, and cytolytic potential. Inhibition of major histocompatibility class II (MHC-II) on target cells or CD4 on CD4(dim)CD8(bright) T cells diminishes their anti-HIV responses, suggesting that CD4 on effector cells and MHC-II on target cells provides an additional arm of contact between effector and target cells which is critical to CD4(dim)CD8(bright) T-cell function. CD4(dim)CD8(bright) T cells also exhibit features that are indicative of central memory T cells. Finally, CD4(dim)CD8(bright) T cells are elevated in blood of HIV+ long-term nonprogressors in comparison to HIV- donors. Collectively, our findings show that CD4(dim)CD8(bright) T cells designate an enriched antiviral subpopulation of CD8+ T cells that should be targeted for therapeutic intervention or evaluation of vaccine efficacy.
Zloza
Andrew
A
Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Schenkel
Jason M
JM
Tenorio
Allan R
AR
Martinson
Jeffrey A
JA
Jeziorczak
Paul M
PM
Al-Harthi
Lena
L
D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use; D000328:Adult; D015704:CD4 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged
D016915:AIDS Vaccines; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II
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