TH1 TH2 CYTOKINE RESPONSES FOLLOWING HIV-1 IMMUNIZATION IN SERONEGATIVE VOLUNTEERS/

The Th1/Th2 profile that follows human vaccination may profoundly infl uence the subsequent course of disease after infection. However, the a bility to detect IL-4 has been limited outside trials of live vaccinat ion. By using methods in which memory effector cells are allowed to an tigenically expand by short term culture, followed by low-dose mitogen ic 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). Antig en-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 im munizations were dominated by IFN-gamma, with IL-4 appearing only afte r 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 dete cted in either study. Such techniques, which have been shown to correl ate with outcomes in immunotherapy, may prove useful as future surroga tes of human vaccine response.