The rat mixed lymphocyte reaction: roles of a dendritic cell in intestinal lymph and T-cell subsets defined by monoclonal antibodies.
Mason DW., Pugh CW., Webb M.
Cells present in the intestinal lymph of rats were obtained in large numbers by removing the mesenteric, portal and caecal lymph nodes and cannulating the thoracic duct 6 weeks later. About 1% of the cells present in the thoracic duct lymph of these mesenteric lymphadenectomized rats had striking dendritic morphology, were strongly Ia+ but labelled weakly with monoclonal antibodies that recognize rat B or T cells. It was found that intestinal lymph was highly enriched for cells that stimulated allogeneic T cells in the mixed lymphocyte reaction (MLR) and cells with stimulator activity co-purified with dendritic cells. Thus, these dendritic cells appear phenotypically and functionally similar to the dendritic cells that have been described in the mouse spleen and rat lymph node. The ability of the intestinal lymph cells to stimulate rat T cells was used to determine which of the two subsets of these cells were the prime responders in the rat MLR. These subsets, defined by monoclonal antibodies, have been shown by previous work to display close functional analogies to the Lyt 2+ and Lyt 2- subsets in the mouse and to the two human T-cell subsets that have been defined by monoclonal antibodies. It was found that the T-cell subset that contains the helper cells for antibody responses proliferated when irradiated, fully allogeneic or semi-allogeneic thoracic duct cells were used as stimulators, but the subset containing suppressor T cells did so only in the fully allogeneic system. Detailed studies showed that in the absence of helper cells in the responder population T cells in the stimulator population of helper phenotype were responsible for proliferation of the suppressor T-cell subset observed in fully allogeneic MLRs. Proliferation of the suppressor T-cell subset could be obtained using semi-allogeneic stimulators, provided that the F1 cells were derived from a source containing dendritic cells but it was shown that, as in the case with fully allogeneic stimulators, the helper T cells in the stimulator population were playing an active role. These results demonstrate that proliferation of the suppressor T-cell subset in the rat MLR is dependent on blastogenic activity provided by the helper T-cell subset and suggest that in some situations this blastogenic activity may arise through the recognition, by the helper cells, of environmental antigens presented on dendritic cells. It has been reported that in the human MLR both T-cell subsets proliferate but that only the helper subset does so when antigen-primed cells are stimulated with specific antigen. The present experiments, by emphasizing the activity of helper T cells in the stimulator population in the MLR, cast doubt on the implication that recognition of alloantigens in vitro differs in an essential way from that of soluble antigens.