Th1/Th2 cytokine responses following HIV-1 immunization in seronegative volunteers. The AIDS Vaccine Evaluation Group.
The Th1/Th2 profile that follows human vaccination may profoundly influence the subsequent course of disease after infection. However, the ability to detect IL-4 has been limited outside trials of live vaccination. By using methods in which memory effector cells are allowed to antigenically expand by short term culture, followed by low-dose mitogenic stimulation, we have been able to follow the Th1/Th2 profile in HIV-1 volunteers enrolled in two phase I studies of HIV immunogens (a recombinant gp120 and a multivalent, octomeric V3 loop peptide). Antigen-specific interferon-gamma (IFN-gamma) could be detected in primary stimulation, but IL-4 was observed only after antigenic expansion and restimulation. In both of these studies the responses after initial immunizations were dominated by IFN-gamma, with IL-4 appearing only after multiple rounds of immunization, and IL-4 was temporally related to antibody production. Concomitant with the IL-4 production, the amount of supernatant IFN-gamma declined. Antigen-specific IL-10 was not detected in either study. Such techniques, which have been shown to correlate with outcomes in immunotherapy, may prove useful as future surrogates of human vaccine response.
Evans
T G
TG
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Fitzgerald
T
T
Gibbons
D C
DC
Keefer
M C
MC
Soucier
H
H
D016915:AIDS Vaccines / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
D016915:AIDS Vaccines; D003470:Culture Media; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D007252:Influenza Vaccines