Human T lymphoblasts and activated dendritic cells in the allogeneic mixed leukocyte reaction are susceptible to NK cell-mediated anti-CD83-dependent cytotoxicity.
CD83 is a marker of dendritic cell (DC) differentiation/activation and its expression in the mouse thymus contributes to CD4(+) T lymphocyte development. Its extrathymic role remains unclear despite the functional effects observed with CD83 fusion proteins or CD83 antibody and recent reports of potential ligands. We investigated the previously observed and presumed functional blockade of the allogeneic mixed leukocyte reaction (MLR) with rabbit polyclonal anti-CD83 (RA83). RA83 inhibition of T lymphocyte proliferation stimulated with allogeneic immature monocyte-derived DC (iMoDC) was confirmed. However, we found it was due to antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells in the responder T cell preparation. The likely targets of the ADCC were MoDC that had up-regulated CD83 during the MLR. Using a (51)Cr-release assay, we confirmed that CD83(+) MoDC, but not CD83(-) MoDC, are lysed by NK cells in the presence of RA83. However, prior fixation of the stimulator MoDC in the allogeneic MLR did not abrogate RA83 inhibition, indicating that cells from the responder T lymphocyte preparation, involved in the MLR proliferative response, also expressed CD83. We found, after 3-4 days of culture with allogeneic MoDC, a subset of CD3(+) cells had up-regulated CD83 and CD25. These were blasting T cells and, when isolated from the MLR, were found to be lysed by autologous NK cells in the presence of RA83. Thus, CD83 is expressed by responding T cells as well as by stimulating cells in the MLR and both are susceptible to anti-CD83-mediated ADCC.
Munster
David J
DJ
Dendritic Cell Laboratory, Mater Medical Research Institute, Brisbane, Queensland 4101, Australia.
MacDonald
Kelli P A
KP
Kato
Masato
M
Hart
Derek J N
DJ
D000906:Antibodies / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000097802:CD83 Antigen
D000906:Antibodies; D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D000097802:CD83 Antigen