EVIDENCE FOR TYPE-2 CYTOKINE PRODUCTION AND LYMPHOCYTE-ACTIVATION IN THE EARLY PHASES OF HIV-1 INFECTION

Objective: To analyse changes in cytokine production in vitro and T-ly mphocyte immunophenotype in the early phases of HIV-1 infection. Desig n and methods: Mitogen-stimulated in vitro production of interferon (I FN)-gamma, interleukin (IL)-2 (type 1 cytokines), IL-4, and IL-10 (typ e 2 cytokines) and surface expression of activation and non-activation markers were evaluated in 11 individuals HIV-infected for >3 but <12 months (seroconverters). The data were compared to those obtained in 3 3 asymptomatic HIV-positive individuals infected >3 years previously a nd who were stratified according to CD4+ lymphocyte count (group 1: >5 00x10(6)/l, group 2: <500x10(6)/l CD4 cells) and in 12 HIV-seronegativ e healthy controls. Results: We observed that the early phase of HIV i nfection is characterized by (1) reduced mitogen-stimulated IL-2 and I FN-gamma production, (2) increased mitogen-stimulated IL-4 and IL-10 p roduction, (3) a relative decrease in CD4+ and CD4+CD7- as well as an increase in CD4+CD7-CD57+ lymphocytes, and (4) a relative increase in CD8+, CD8+CD38+ and CD8+CD57+ T lymphocytes. In addition, during a 6-m onth follow-up of six seroconverters we observed a dynamic pattern of changes of these parameters in most individuals, with a resulting prof ile similar to that observed in group 1 HIV-positive patients. Conclus ion: The early phase of HIV infection is immunologically characterized by type 2 cytokine secretion and alterations in the expression of phe notypic markers, and closely resembles the more advanced phases of HIV infection. These immunologic alterations are temporally limited by th e successive return to a more normal profile. Thus, HIV infection is a n immunological complex dynamic process even in its earliest phases.