Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens.
CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.
Ho
H N
HN
Department of Medicine, University of California, Los Angeles 90024-1745.
Hultin
L E
LE
Mitsuyasu
R T
RT
Matud
J L
JL
Hausner
M A
MA
Bockstoce
D
D
Chou
C C
CC
O'Rourke
S
S
Taylor
J M
JM
Giorgi
J V
JV
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D016827:CD8 Antigens / Q000097:blood*; D003602:Cytotoxicity, Immunologic; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006684:HLA-DR Antigens / Q000097:blood* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008562:Membrane Glycoproteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D016827:CD8 Antigens; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1