MHC CLASS I+ II- DENDRITIC CELLS INDUCE HAPTEN-SPECIFIC IMMUNE-RESPONSES IN-VITRO AND IN-VIVO/

Activation requirements and biologic properties of hapten-specific, ma jor histocompatibility complex class I-restricted CD8(+) T lymphocytes are not fully understood. To address this issue, a novel CD45(+)/majo r histocompatibility complex class I+(H-2(k))/II-/CD80(+) dendritic ce ll line, termed 80/1, which is capable of stimulating naive, allogenei c CD8(+) but not CD4(+) T cells in vitro, was derivatized with trinitr obenzenesulfonic acid and co-cultured for 4 d with syngeneic, naive CD 8(+) T cells. Results obtained showed that trinitrophenyl-derivatized, but not underivatized 80/1 dendritic cells, can induce vigorous proli feration of CD8(+) T cells. T-cell blasts generated in this fashion we re able to lyse syngeneic, trinitrophenyl-derivatized targets but fail ed to lyse underivatized or trinitrophenyl-derivatized syngeneic, majo r histocompatibility complex class I- mutant cells or allogeneic targe ts. The ability of 80/1 dendritic cells to prime naive, syngeneic T ce lls in vivo was tested in a contact hypersensitivity model. C3H/HeN mi ce were injected subcutaneously with identical numbers of (i) trinitro phenyl-derivatized 80/1 dendritic cells; (ii) trinitrophenyl-derivatiz ed 80/1 dendritic cells fragmented by freeze-thawing cycles; (iii) tri nitrophenyl-derivatized fibrosarcoma L929; and (iv) trinitrophenyl-der ivatized lymphoma R1.1 cells. Whereas live trinitrophenyl-derivatized 80/1 dendritic cells were able to sensitize for contact hypersensitivi ty, killed hapten-derivatized 80/1 dendritic cells or control cells fa iled to do so. Thus, we conclude that 80/1 dendritic cells, when compa red with major histocompatibility complex class I+ non-dendritic cells , can effectively prime naive, syngeneic CD8(+) T cells for hapten-spe cific responses, probably due to their better costimulatory and migrat ory properties.