CD8⁺ T cells that express CD4 on their surface (CD4 ^dimCD8^bright 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 ^dimCD8^bright phenotype. We previously demonstrated that the CD4^dimCD8^bright phenotype constitutes an activated phenotype of CD8⁺ T cells. We demonstrate here that the activated CD4^dimCD8^bright T cells are not undergoing apoptosis and do not produce significant intracellular levels of interferon γ (IFNγ), 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, CD4^dimCD8^bright 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. CD4 ^dimCD8^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 β-chemokine is responsible for the inhibition of M-tropic HIV infection in CD4^dimCD8^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^dimCD8^bright T cells in HIV⁺ patients, albeit at low frequency. Collectively, these data suggest a role of CD4 ^dimCD8^bright T cells in both normal T-cell biology and HIV pathogenesis.