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Journal of Virology, August 2004, p. 8844-8851, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8844-8851.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Beyond Help: Direct Effector Functions of Human Immunodeficiency Virus Type 1-Specific CD4⁺ T Cells

Blood Systems Research Institute, San Francisco, California 94118,¹ Partners AIDS Research Center, Massachusetts General Hospital Division of Infectious Diseases and Harvard Medical School, Charlestown, Massachusetts 02129,² Division of Infectious Diseases/Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, AIDS Institute, Geffen School of Medicine, UCLA Medical Center, Los Angeles, California, 90095³

Received 19 February 2004/ Accepted 13 April 2004

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.

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