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

CD4 can be up-regulated on CD8(+) T cells generating a CD4(dim)CD8(bright) phenotype. We previously demonstrated that the CD4(dim)CD8(bright) phenotype constitutes an activated phenotype of CD8(+) T cells. We demonstrate here that the activated CD4(dim)CD8(bright) T cells are not undergoing apoptosis and do not produce significant intracellular levels of interferon gamma (IFNgamma), 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 cytomegalo-virus (CMV) peptide (pp65) priming, CD4(dim)CD8(bright) cells recognized CMV pp65 tetramer approximately 19-fold higher than CD4(-)CD8(+) T cells, indicating that these cells are capable of antigen-pecific recognition to a far greater extent than CD4(-)CD8(+) T cells. CD4(dim)CD8(bright) 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 beta-chemokine is responsible for the inhibition of M-tropic HIV infection in CD4(dim)CD8(bright) 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 CD4(dim)CD8(bright) T cells in HIV+ patients, albeit at low frequency. Collectively, these data suggest a role of CD4(dim)CD8(bright) T cells in both normal T-cell biology and HIV pathogenesis. (C) 2003 by The American Society of Hematology.