Differential requirements of MHC and of DCs for endogenous proliferation of different T-cell subsets in vivo.
T cells transferred into severe lymphopenic hosts undergo rapid proliferation known as "endogenous proliferation" that are distinct from conventional homeostatic proliferation. Unlike homeostatic proliferation, cytokines, such as IL-7 are dispensable, yet TCR:MHC interaction is essential for this process to occur. However, cell types inducing the proliferation have not formally been addressed. In this study, we report that CD11c+ conventional DCs play irreplaceable roles in inducing endogenous proliferation of both naive and memory phenotype CD4 T cells via TCR-MHC II interaction. By contrast, CD8 T-cell endogenous proliferation was independent of MHC I or CD11c+ DCs. Interestingly, MHC II was necessary to support naive CD8 T-cell proliferation within MHC I-deficient hosts. Depletion of both B cells and DCs was sufficient to abrogate the proliferation of naive but not of memory CD8 T cells. These results suggest that depending on the T-cell lineages, as well as the differentiation status, different mechanisms control endogenous proliferation, revealing in vivo complexity of T-cell proliferation under lymphopenic conditions.
Do
Jeong-su
JS
Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Min
Booki
B
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D039521:CD11c Antigen