An activated CD8+ T cell phenotype correlates with anti-HIV activity and asymptomatic clinical status.
We have examined the relation of cell surface marker phenotype to the anti-human immunodeficiency virus (HIV) function of CD8+ cells from individuals at various clinical stages of HIV infection. Multiparametric flow cytometry analysis demonstrated that the most significant changes in cell surface phenotype was found within the CD8+ cell subset expressing HLA-DR and CD28. These changes in the levels of CD28 and HLA-DR expression on CD8+ cells were found to be related to antiviral activity and have clinical relevance based on three pieces of evidence: (1) strong CD8+ cell antiviral responses were associated in infected individuals with high levels of HLA-DR+ and CD28+ subsets; (2) CD8+ cell anti-HIV activity in vitro resides predominantly in the separated CD8+ cell subsets that express HLA-DR or CD28; and (3) in longitudinal studies, CD8+ cell anti-HIV activity decreased as an individual progressed from a healthy state to an AIDS condition. Taken together, the data suggest that the CD8+ cell subset identified phenotypically as a CD8+ CD28+ HLA-DR+ cell is responsible for natural anti-HIV activity. Longitudinal studies should determine if alterations in this subset can be used as a prognostic indicator for disease progression.
Landay
A L
AL
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864.
Mackewicz
C E
CE
Levy
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology; D000998:Antiviral Agents / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication
D000998:Antiviral Agents; D018106:CD28 Antigens; D016827:CD8 Antigens; D015483:HIV Antibodies; D006684:HLA-DR Antigens