Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis.
The lymphocyte proliferative response to recall antigens is lost following HIV infection. We sought to devise a means by which the functional immune status of persons in the early stages of HIV infection could be monitored quantitatively. The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. Our data show that the limiting dilution analysis detects tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44% by proliferation. However, the frequency of tetanus-reactive T cells in HIV-infected individuals (median frequency = 1/59,156) is decreased five-fold as compared to seronegative controls (median frequency = 1/11,599). Longitudinal studies demonstrated a time-dependent decrease in the frequency of tetanus-specific T cell responses in the HIV-infected individuals. Thus, the limiting dilution analysis is a quantitative approach for detecting antigen-specific T cells in HIV-infected individuals, and may be used to monitor changes in T cell function in HIV infection.
Sabbaj
S
S
Department of Medical Microbiology and Immunology, Ohio State University, Columbus 43210.
Para
M F
MF
Fass
R J
RJ
Adams
P W
PW
Orosz
C G
CG
Whitacre
C C
CC
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007158:Immunologic Techniques; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*
D000939:Epitopes; D007376:Interleukin-2; D013745:Tetanus Toxoid