Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

• Published in: The Journal of immunology (1950) 2005-03, Vol.174 (5), p.2900-2909
• Main Authors: Paiardini, Mirko, Cervasi, Barbara, Albrecht, Helmut, Muthukumar, Alagarraju, Dunham, Richard, Gordon, Shari, Radziewicz, Henry, Piedimonte, Giuseppe, Magnani, Mauro, Montroni, Maria, Kaech, Susan M, Weintrob, Amy, Altman, John D, Sodora, Donald L, Feinberg, Mark B, Silvestri, Guido
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis - immunology; Biomarkers - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation; Disease Progression; Disease Susceptibility - immunology; Dose-Response Relationship, Immunologic; Epitopes, T-Lymphocyte - immunology; Female; Gene Products, gag - immunology; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; HIV-1 - immunology; Humans; Immunologic Memory; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Lymphocyte Activation - immunology; Male; Middle Aged; Receptors, Interleukin-7 - biosynthesis; Receptors, Interleukin-7 - deficiency; Receptors, Interleukin-7 - genetics; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.5.2900

The immunodeficiency that follows HIV infection is related to the virus-mediated killing of infected CD4(+) T cells, the chronic activation of the immune system, and the impairment of T cell production. In this study we show that in HIV-infected individuals the loss of IL-7R (CD127) expression defines the expansion of a subset of CD8(+) T cells, specific for HIV as well as other Ags, that show phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in activated and/or proliferating cells) as well as functional (i.e., production of IFN-gamma, but not IL-2, decreased ex vivo proliferative potential and increased susceptibility to apoptosis) features of effector T cells. Importantly, in HIV-infected individuals the levels of CD8(+)CD127(-) T cells are directly correlated with the main markers of disease progression (i.e., plasma viremia and CD4(+) T cell depletion) as well as with the indices of overall T cell activation. In all, these results identify the expansion of CD8(+)CD127(-) effector-like T cells as a novel feature of the HIV-associated immune perturbation. Further studies are thus warranted to determine whether measurements of CD127 expression on CD8(+) T cells may be useful in the clinical management of HIV-infected individuals.