Loss of CD127 expression defines an expansion of effector CD8+ T cells in HIV-infected individuals.
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.
Paiardini
Mirko
M
Department of Medicine, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cervasi
Barbara
B
Albrecht
Helmut
H
Muthukumar
Alagarraju
A
Dunham
Richard
R
Gordon
Shari
S
Radziewicz
Henry
H
Piedimonte
Giuseppe
G
Magnani
Mauro
M
Montroni
Maria
M
Kaech
Susan M
SM
Weintrob
Amy
A
Altman
John D
JD
Sodora
Donald L
DL
Feinberg
Mark B
MB
Silvestri
Guido
G
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D004198:Disease Susceptibility / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D007376:Interleukin-2; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma