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

Andrew Zloza, Jason M. Schenkel, Allan R. Tenorio, Jeffrey A. Martinson, Paul M. Jeziorczak, Lena Al-Harthi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

In humans, approximately 3% of peripheral CD8+ T cells coexpress CD4 dimly on their surface and hence are designated as CD4 dimCD8bright 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 CD4dimCD8 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 dimCD8bright T-cell function. CD4dimCD8 bright 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 CD4 dimCD8bright T cells designate an enriched antiviral subpopulation of CD8+ T cells that should be targeted for therapeutic intervention or evaluation of vaccine efficacy.

Original languageEnglish (US)
Pages (from-to)3841-3853
Number of pages13
JournalBlood
Volume114
Issue number18
DOIs
StatePublished - Oct 29 2009
Externally publishedYes

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