CD8alpha+ and CD11b+ dendritic cell-restricted MHC class II controls Th1 CD4+ T cell immunity.
The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to the development of type I immune responses. MHC class II (MHCII)-bearing dendritic cells (DCs) initiate CD4(+) T cell priming, but the relative contributions of other MHCII(+) APCs to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-A(beta)(b) expression was targeted specifically to the DCs of I-A(beta)b-/- mice. MHCII expression is reconstituted in CD11b(+) and CD8alpha(+) DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells lack of expression of the I-A(beta)(b) chain. Presentation of both peptide and protein Ags by these DC subsets is sufficient for Th1 differentiation of Ag-specific CD4(+) T cells in vivo. Thus, Ag-specific CD4(+) T cells are primed to produce Th1 cytokines IL-2 and IFN-gamma. Additionally, proliferation, migration out of lymphoid organs, and the number of effector CD4(+) T cells are appropriately regulated. However, class II-negative B cells cannot receive help and Ag-specific IgG is not produced, confirming the critical MHCII requirement at this stage. These findings indicate that DCs are not only key initiators of the primary response, but provide all of the necessary cognate interactions to control CD4(+) T cell fate during the primary immune response.
Lemos
Maria P
MP
Department of Medicine, University of Pennsylvania, Philadelphia PA 19104, USA.
Fan
Lian
L
Lo
David
D
Laufer
Terri M
TM
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D039481:CD11b Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D010047:Ovalbumin