During HIV infection, CD4+ CD38+ T-cells are the predominant circulating CD4+ subset whose HLA-DR positivity increases with disease progression and whose V beta repertoire is similar to that of CD4+ CD38- T-cells.
Three-color automated flow cytometry was carried out on peripheral blood CD4+ and CD8+ T-lymphocytes of 42 HIV-positive patients using tri-color anti-CD4 or anti-CD8, phycoerythrin-anti-CD38, and fluorescein-anti-HLA-DR, mAbs to elucidate further the T-cell activation hypothesis recently proposed to explain CD4+ T-cell abnormalities observed during HIV infection. CD4+ CD38+ T-cells constituted the major part of circulating CD4+ T-cells in HIV-infected patients and their HLA-DR molecule positivity increased as their disease progressed. The level of CD38 and HLA-DR expression on CD4+ T-cells was positively correlated to that of CD8+ T-cells and to the level of beta 2-microglobulin. Next, to determine whether CD38 expression was associated with a selective expansion or deletion of V beta gene-defined subsets, we compared the V beta gene frequencies between CD38+ and CD38- T-cells from HIV-infected CDC stage II patients using 13 mAbs specific to V beta families. While selective expansion of certain V beta families was observed in CD4+ and CD8+ T-cells the T-cell receptor V beta subset distribution was similar among CD38+ and CD38-, CD4+ and CD8+ T-cells, suggesting that CD38+ expression was either independent of an HIV-encoded antigen-driven process or rather indicative of T-cell immaturity. It is proposed that the phenotype of circulating CD4+ and CD8+ T-cells of HIV-infected patients is a feature of two different mechanisms: (i) an in vitro activation state responsible for increased DR expression and selective expansion of V beta gene-defined subsets, and (ii) T-cell immaturity due to an increased turnover of these cells and accounting for increased CD38 expression.
Ramzaoui
S
S
Groupe de Recherche en Immunopathologie, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, France.
Jouen-Beades
F
F
Gilbert
D
D
Borsa-Lebas
F
F
Michel
Y
Y
Humbert
G
G
Tron
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015215:Zidovudine / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D015215:Zidovudine; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1