The influence of lymphocyte counts and disease progression on circulating and inducible anti-HIV-1 cytotoxic T-cell activity in HIV-1-infected subjects.
OBJECTIVE
To evaluate specific anti-HIV cytotoxic T-lymphocyte (CTL) activity in relation to basic clinical and laboratory parameters used to follow HIV infection.


METHODS
Lymphocytes from HIV-1-infected subjects with different clinical and immunologic features of HIV infection were tested for circulating and inducible anti-HIV CTL activity using autologous B-lymphoblastoid cells infected with recombinant vaccinia viruses expressing the HIV gag, pol and env genes as targets. Anti-HIV CTL were induced by stimulation with HIV-infected autologous lymphoblasts in vitro.


RESULTS
We detected circulating anti-HIV CTL in asymptomatic subjects exclusively and found a significant association (P < 0.01) between CD8+ lymphocyte counts > or = 900/microliters blood and detectable levels of circulating anti-HIV CTL. Subjects with circulating anti-HIV CTL also had a higher mean CD8+ lymphocyte count than those without detectable circulating activity (P < 0.001), but there was no significant difference in mean CD4+ lymphocyte count. CD8+ human histocompatibility leukocyte antigen (HLA) class I-restricted anti-HIV CTL were induced in all HIV-infected subjects tested following stimulation with HIV-infected autologous lymphoblasts in vitro. In subjects without detectable circulating anti-HIV CTL, circulating HLA-DR+ cells contributed to anti-HIV CTL activity induced by stimulation with HIV or concanavalin A in vitro.


CONCLUSIONS
Circulating anti-HIV CTL activity is associated with CD8+ lymphocyte counts > or = 900/microliters. Anti-HIV CTL retain proliferative and functional capacity following in vitro stimulation with HIV and interleukin-2 through all stages of HIV infection. Persistent inducible anti-HIV CTL activity in subjects with advanced HIV disease and without circulating CTL suggests impaired activation and/or proliferation of the CTL in vivo.
Grant
M D
MD
Department of Pathology, McMaster University Health Sciences Center, Hamilton, Ontario, Canada.
Smaill
F M
FM
Singal
D P
DP
Rosenthal
K L
KL
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005805:Genes, MHC Class I; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D016827:CD8 Antigens; D006680:HLA Antigens; D007376:Interleukin-2