CD1d1-dependent control of the magnitude of an acute antiviral immune response

被引:43
作者
Roberts, TJ
Lin, YL
Spence, PM
Van Kaer, L
Brutkiewicz, RR
机构
[1] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[2] Walther Oncol Ctr, Indianapolis, IN 46202 USA
[3] Walther Canc Inst, Indianapolis, IN 46208 USA
[4] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
关键词
D O I
10.4049/jimmunol.172.6.3454
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD1d1-restricted NK T (NKT) cells rapidly secrete both Th1 and Th2 cytokines upon activation and are therefore thought to play a regulatory role during an immune response. In this study we examined the role of CD1d1 molecules and NKT cells in regulating virus-induced cytokine production. CD1d1-deficient (CD1KO) mice, which lack NKT cells, were infected with lymphocytic choriomeningitis virus, and spontaneous cytokine release from splenocytes was measured. We found that CD1KO mice produce significantly higher amounts of IL-2, IL-4, and IFN-gamma compared with wild-type controls postinfection. Depletion studies of individual lymphocyte subpopulations suggested that CD4(+) T cells are required; however, isolation of specific lymphocyte populations indicated that CD4(+) T cells alone are not sufficient for the increase in cytokine production in CD1KO mice. Splenocytes from lymphocytic choriomeningitis virus-infected CD1KO mice continued to produce enhanced cytokine levels long after viral clearance and cleared viral RNA faster than wild-type mice. There was no difference in the number of splenocytes between uninfected wild-type and CD1KO mice, whereas the latter knockout mice had an increased number of splenocytes after infection. Collectively, these data provide clear evidence that the expression of CD1d1 molecules controls the magnitude of the cell-mediated immune response to an acute viral infection.
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页码:3454 / 3461
页数:8
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