Subsets of T Cells in the Rat Mediating Lethal Graft-Versus-Host Disease

Mouse monoclonal antibodies that recognize rat thymocyte membrane antigens have been shown to define two nonoverlapping subsets of rat peripheral T cells. Earlier studies have shown that these T cell subsets mediate different immunological functions and are probably analogous to the Lyt-2+ and Lyt-2- subsets in the mouse. This paper reports the activity of these two T cell subsets in mediating graft-versus-host disease (GVHD) in rats and examines the role played by donor B cells. Parental strain thoracic duct lymphocytes were depleted of one or other of the two subsets and the residual cells transferred to sublethally irradiated F1 recipients. With one subset, which is known to contain the precursors of cytotoxic T cells, the disease, although usually fatal, tended to run a rather protracted course. In contrast, the subset containing helper T cells and cells that proliferate strongly in the mixed lymphocyte reaction caused a disease that was as rapidly fatal as that resulting from the injection of unfractionated donor cells. The activity of this subset was uninfluenced by the presence or absence of donor B cells. Recipients of parental lymphocytes depleted of both T cell subsets showed no evidence of disease and gained weight at the same rate as rats given no parental cells. I concluded that GVHD can be mediated by more than one type of effector T cell and, although cytotoxic T cells of donor origin may be capable of mediating lethal GVHD, these cells play no indispensable role in this condition.