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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-07-1972.
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Blood, 15 September 2003, Vol. 102, No. 6, pp. 2156-2164
IMMUNOBIOLOGY
CD8+ T cells that express CD4 on their surface (CD4dimCD8bright T cells) recognize an antigen-specific target, are detected in vivo, and can be productively infected by T-tropic HIV
Andrew Zloza,
Yvonne B. Sullivan,
Elizabeth Connick,
Alan L. Landay, and
Lena Al-Harthi
From the Department of Immunology and Microbiology, Rush-Presbyterian-St Luke's Medical Center, Rush University, Chicago, IL; and the Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver.
CD4 can be up-regulated on CD8+ T cells generating a CD4dimCD8bright phenotype. We previously demonstrated that the CD4dimCD8bright phenotype constitutes an activated phenotype of CD8+ T cells. We demonstrate here that the activated CD4dimCD8bright T cells are not undergoing apoptosis and do not produce significant intracellular levels of interferon  (IFN), interleukin 2 (IL-2), or IL-10 but express elevated levels of intracellular IL-4 in comparison to CD8+CD4– and CD4+ T cells. In response to cytomegalovirus (CMV) peptide (pp65) priming, CD4dimCD8bright cells recognized CMV pp65 tetramer approximately 19-fold higher than CD4–CD8+ T cells, indicating that these cells are capable of antigen-specific recognition to a far greater extent than CD4–CD8+ T cells. CD4dimCD8bright T cells also express both CXCR4 and CCR5 but are susceptible to T-tropic and not M-tropic HIV infection. A soluble factor believed to be  -chemokine is responsible for the inhibition of M-tropic HIV infection in CD4dimCD8bright T cells. CD8+ T cells from HIV+ patients were capable of up-regulating CD4 on CD8+ T cells. We also provide evidence of the presence of peripheral blood CD4dimCD8bright T cells in HIV+ patients, albeit at low frequency. Collectively, these data suggest a role of CD4dimCD8bright T cells in both normal T-cell biology and HIV pathogenesis.
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