The TRAIL of helpless CD8+ T cells in HIV infection.
Our understanding of how CD4(+) T cells can regulate CD8(+) T cell responses in HIV infection is still incomplete. Recent evidence obtained in mice suggests that CD4(+) T cell help is required for efficient CD8(+) T cell-mediated immunity in chronic infection: CD8(+) T cells primed in the absence of such help release the TNF-related apoptosis-inducing ligand TRAIL and undergo apoptosis. Using a novel ELISPOT assay, in the present study we show that CD8(+) T cells are also a source of the antigen-specific TRAIL response in HIV-infected patients with CD4(+) T cell counts below 200. In patients with CD4(+) T cell counts above 200 TRAIL was not detectable. Accordingly, antigens to which patients have likely been exposed when CD4(+) T cell levels were high (e.g., influenza, CMV, and EBV) did not induce TRAIL. Within the HIV-positive donor population with low CD4(+) T cell counts a dissociation of the interferon-gamma (IFN-gamma) and TRAIL response to different HIV peptide epitopes was detectable suggesting impaired immunity to antigens that triggered TRAIL in the absence of IFN-gamma. Our findings emphasize that "helpless" CD8(+) T cells, i.e., cells that have been primed in the absence of CD4(+) T cell help, may play a crucial role in HIV infection. A "helpless" phenotype may impair CD8(+) T cell control of HIV and other infections and possibly contribute to the depletion of CD4(+) T cells via apoptosis. Immunizations and infections in this "helpless" state might result in ineffective CD8(+) T cell responses.
Kuerten
Stefanie
S
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Asaad
Robert J
RJ
Schoenberger
Stephen P
SP
Angelov
Doychin N
DN
Lehmann
Paul V
PV
Tary-Lehmann
Magdalena
M
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*; D019562:Viral Load
D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D007371:Interferon-gamma