MHC class I+/II- dendritic cells induce hapten-specific immune responses in vitro and in vivo

Abstract

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-2(κ))/II-/CD80+ dendritic cell line, termed 80/1, which is capable of stimulating naive, allogeneic CD8+ but not CD4+ T cells in vitro, was derivatized with trinitrobenzenesulfonic acid and co-cultured for 4 d with syngeneic, naive CD8+ T cells. Results obtained showed that trinitrophenylderivatized, but not underivatized 80/1 dendritic cells, can induce vigorous proliferation of CD8+ 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 naive, 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 naive, syngeneic CD8+ T cells for hapten-specific responses, probably due to their better costimulatory and migratory properties.