Preferential Th1 immune response in invariant chain-deficient mice.
MHC class II molecules associate with the invariant chain (Ii) molecule during biosynthesis. Ii facilitates the folding of class II molecules, interferes with their peptide association, and is involved in MHC class II transport. In this study, we have investigated the in vitro and in vivo immune response of Ii-deficient mice (Ii(-/-)). Our results have demonstrated that CD4(+) T cells from Ii(-/-) mice proliferate normally in vitro after in vivo immunization with protein Ags. However, cytokine secretion profiles of Ag-primed CD4(+) T cells from Ii(-/-) mice differ from CD4(+) T cells from wild-type mice. Whereas cells from wild-type mice secrete IFN-gamma and IL-4, cells from Ii(-/-) mice secrete mostly IFN-gamma. Moreover, Ii(-/-) mice exhibit a normal Th1 response in the delayed-type hypersensitivity and trinitrobenzene sulfonic acid colitis models; however, these mice lack an in vivo Th2 response, as demonstrated in the asthma model. Therefore, we suggest that defective Ag presentation in Ii(-/-) mice leads selectively to a Th1 effector response.
Topilski
Ian
I
Department of Immunology and Experimental Animal Center, The Weizmann Institute of Science, Rehovot, Israel.
Harmelin
Alon
A
Flavell
Richard A
RA
Levo
Yoram
Y
Shachar
Idit
I
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008934:Mitogens; C045084:invariant chain