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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3841-3853.
Prepublished online as a Blood First Edition Paper on September 18, 2009; DOI 10.1182/blood-2009-02-202481.


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IMMUNOBIOLOGY

Potent HIV-specific responses are enriched in a unique subset of CD8+ T cells that coexpresses CD4 on its surface

Andrew Zloza1, Jason M. Schenkel1, Allan R. Tenorio2, Jeffrey A. Martinson1, Paul M. Jeziorczak1, and Lena Al-Harthi1

Departments of 1 Immunology/Microbiology and 2 Internal Medicine, Rush University Medical Center, Chicago, IL

In humans, approximately 3% of peripheral CD8+ T cells coexpress CD4 dimly on their surface and hence are designated as CD4dimCD8bright T cells. We evaluated the contribution of this CD4dimCD8bright T-cell population to anti-HIV immunity. We demonstrate that CD4dimCD8bright 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 CD4dimCD8bright 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 CD4dimCD8bright T-cell function. CD4dimCD8bright T cells also exhibit features that are indicative of central memory T cells. Finally, CD4dimCD8bright T cells are elevated in blood of HIV+ long-term nonprogressors in comparison to HIV donors. Collectively, our findings show that CD4dimCD8bright T cells designate an enriched antiviral subpopulation of CD8+ T cells that should be targeted for therapeutic intervention or evaluation of vaccine efficacy.


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