CYTOKINES AND IMPAIRED CD8(-12() CTL ACTIVITY AMONG ELDERLY PERSONS AND THE ENHANCING EFFECT OF IL)

We have previously demonstrated that about 70% of elderly persons exhi bit deficient cytotoxic T lymphocyte (CD8(+) CTL) responses against in fluenza viruses when compared to young persons. Since IFN-gamma, a Th1 cytokine and IL-4, a Th2 cytokine, stimulate and inhibit CD8(+) CTL r esponses respectively, their role(s) in the age-related CTL deficiency was investigated. Lymphocytes from young adults (34 +/- 5 years old) and elderly subjects (71 +/- I years old) were stimulated in vitro wit h influenza A/H3N2, A/H1N1 or influenza B virus for 6-7 days. The CD8( +) CTL activity against virus-infected autologous target cells was sig nificantly lower among the elderly than the young subjects (P < 0.01). Following stimulation with influenza virus, IL-4 production in both a ge groups was similar on day 3 but significantly higher among elderly persons on day 6 (P < 0.05). In contrast, T cells from the elderly pro duced significantly lower IFN-gamma than did those from young persons on both days (P < 0.05). Treatment of T cells from young and elderly a dults with recombinant human IL-12, a pivotal cytokine that stimulates Th1 cytokines, resulted in enhancement of CD8(+) CTL activity and IFN -gamma production in a dose dependent manner (P < 0.01). IL-12-depende nt enhancement of CTL activity was not always abrogated by anti-IFN-ga mma antibody treatment. These results suggest that deficient influenza virus-specific CTL activity among the elderly is attributable to a Th 1 to Th2 cytokine production switch. Immunotherapy with IL-12 could re present a useful approach to correct the CD8(+) CTL deficiency and cyt okine imbalance among elderly humans. (C) 1997 Elsevier Science Irelan d Ltd.