MHC class I+/II- dendritic cells induce hapten-specific immune responses in vitro and in vivo.
Activation requirements and biologic properties of hapten-specific, major histocompatibility complex class I-restricted CD8+ T lymphocytes are not fully understood. To address this issue, a novel CD45+/major histocompatibility complex class I+ (H-2k)/II-/CD80+ dendritic cell line, termed 80/1, which is capable of stimulating naïve, allogeneic CD8+ but not CD4+ T cells in vitro, was derivatized with trinitrobenzenesulfonic acid and co-cultured for 4 d with syngeneic, naïve CD8+ T cells. Results obtained showed that trinitrophenyl-derivatized, but not underivatized 80/1 dendritic cells, can induce vigorous proliferation ofCD8+ T cells. T-cell blasts generated in this fashion were able to lyse syngeneic, trinitrophenyl-derivatized targets but failed to lyse underivatized or trinitrophenyl-derivatized syngeneic, major histocompatibility complex class I- mutant cells or allogeneic targets. The ability of 80/1 dendritic cells to prime naïve, syngeneic T cells in vivo was tested in a contact hypersensitivity model. C3H/HeN mice were injected subcutaneously with identical numbers of (i) trinitrophenyl-derivatized 80/1 dendritic cells; (ii) trinitrophenyl-derivatized 80/1 dendritic cells fragmented by freeze-thawing cycles; (iii) trinitrophenyl-derivatized fibrosarcoma L929; and (iv) trinitrophenyl-derivatized lymphoma R1.1 cells. Whereas live trinitrophenyl-derivatized 80/1 dendritic cells were able to sensitize for contact hypersensitivity, killed hapten-derivatized 80/1 dendritic cells or control cells failed to do so. Thus, we conclude that 80/1 dendritic cells, when compared with major histocompatibility complex class I+ non-dendritic cells, can effectively prime naïve, syngeneic CD8+ T cells for hapten-specific responses, probably due to their better costimulatory and migratory properties.
Kolesaric
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Department of Dermatology, University of Vienna Medical School, Vienna International Research Cooperation Centre, Austria.
Stingl
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Elbe-Bürger
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D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007114:Immunization; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014301:Trinitrobenzenes / Q000494:pharmacology
D006241:Haptens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014301:Trinitrobenzenes