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 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 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 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 beta-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.
Zloza
Andrew
A
Department of Immunology and Microbiology, Rush-Presbyterian-St Luke's Medical Center, 1735 W Harrison Street, 614 Cohn, Chicago, IL 60612, USA.
Sullivan
Yvonne B
YB
Connick
Elizabeth
E
Landay
Alan L
AL
Al-Harthi
Lena
L
D000954:Antigens, Surface / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D000939:Epitopes; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012995:Solubility; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000954:Antigens, Surface; D015704:CD4 Antigens; D000939:Epitopes; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015847:Interleukin-4