Cytokines and impaired CD8(+) CTL activity among elderly persons and the enhancing effect of IL-12

被引:54
作者
Mbawuike, IN
Acuna, CL
Walz, KC
Atmar, RL
Greenberg, SB
Couch, RB
机构
关键词
Th1; cytokine; Th2; CD8(+) CTL deficiency; elderly humans;
D O I
10.1016/S0047-6374(96)01855-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have previously demonstrated that about 70% of elderly persons exhibit deficient cytotoxic T lymphocyte (CD8(+) CTL) responses against influenza viruses when compared to young persons. Since IFN-gamma, a Th1 cytokine and IL-4, a Th2 cytokine, stimulate and inhibit CD8(+) CTL responses 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 with influenza A/H3N2, A/H1N1 or influenza B virus for 6-7 days. The CD8(+) CTL activity against virus-infected autologous target cells was significantly lower among the elderly than the young subjects (P < 0.01). Following stimulation with influenza virus, IL-4 production in both age 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 produced significantly lower IFN-gamma than did those from young persons on both days (P < 0.05). Treatment of T cells from young and elderly adults 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-dependent enhancement of CTL activity was not always abrogated by anti-IFN-gamma antibody treatment. These results suggest that deficient influenza virus-specific CTL activity among the elderly is attributable to a Th1 to Th2 cytokine production switch. Immunotherapy with IL-12 could represent a useful approach to correct the CD8(+) CTL deficiency and cytokine imbalance among elderly humans. (C) 1997 Elsevier Science Ireland Ltd.
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页码:25 / 39
页数:15
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