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-lymphocyte immunophenotype in the early phases of HIV-1 infection. Design and methods: Mitogen-stimulated in vitro production of interferon (IFN)-gamma, interleukin (IL)-2 (type 1 cytokines), IL-4, and IL-10 (type 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 33 asymptomatic HIV-positive individuals infected >3 years previously and who were stratified according to CD4+ lymphocyte count (group 1: >500x10(6)/l, group 2: <500x10(6)/l CD4 cells) and in 12 HIV-seronegative healthy controls. Results: We observed that the early phase of HIV infection is characterized by (1) reduced mitogen-stimulated IL-2 and IFN-gamma production, (2) increased mitogen-stimulated IL-4 and IL-10 production, (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-month follow-up of six seroconverters we observed a dynamic pattern of changes of these parameters in most individuals, with a resulting profile similar to that observed in group 1 HIV-positive patients. Conclusion: The early phase of HIV infection is immunologically characterized by type 2 cytokine secretion and alterations in the expression of phenotypic markers, and closely resembles the more advanced phases of HIV infection. These immunologic alterations are temporally limited by the successive return to a more normal profile. Thus, HIV infection is an immunological complex dynamic process even in its earliest phases.