CD1d1-dependent control of the magnitude of an acute antiviral immune response.
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.
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202, USA.
Tonya J
TJ
Roberts
Yinling
Y
Lin
Philip M
PM
Spence
Luc
L
Van Kaer
Randy R
RR
Brutkiewicz
D000208:Acute Disease; D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055610:Antigens, CD1d; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma