Beyond help: direct effector functions of human immunodeficiency virus type 1-specific CD4(+) T cells.
The immune correlates of protection in human immunodeficiency virus type 1 (HIV-1) infection remain poorly defined, particularly the contribution of CD4(+) T cells. Here we explore the effector functions of HIV-1-specific CD4(+) T cells. We demonstrate HIV-1 p24-specific CD4(+)-T-cell cytolytic activity in peripheral blood mononuclear cells directly ex vivo and after enrichment by antigen-specific stimulation. We further show that in a rare long-term nonprogressor, both an HIV-1-specific CD4(+)-T-cell clone and CD4(+) T cells directly ex vivo exert potent suppression of HIV-1 replication. Suppression of viral replication was dependent on cell-cell contact between the effector CD4(+) T cells and the target cells. While the antiviral effector activity of CD8(+) T cells has been well documented, these results strongly suggest that HIV-1-specific CD4(+) T cells are capable of directly contributing to antiviral immunity.
Blood Systems Research Institute, 270 Masonic Ave., San Francisco, CA 94118, USA. pnorris@bloodsystems.org
Philip J
PJ
Norris
Howell F
HF
Moffett
Otto O
OO
Yang
Daniel E
DE
Kaufmann
Margaret J
MJ
Clark
Marylyn M
MM
Addo
Eric S
ES
Rosenberg
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D016655:HIV Core Protein p24