The graft-versus-host reaction and immune function. I. T helper cell immunodeficiency associated with graft-versus-host-induced thymic epithelial cell damage.

The injection of parental A strain lymphoid cells into adrenalectomized CBAxA F1 (BAF1) mice induced a chronic graft-versus-host (GVH) reaction resulting in T cell and B cell immunosuppression as well as thymic epithelial cell injury, but not stress-related thymic involution. Thymocytes from BAF1 mice undergoing a GVH reaction were studied for their ability to reconstitute T helper cell (TH) function and phytohemagglutinin (PHA) and concanavalin A (Con A) mitogen responses in thymectomized, irradiated, BAF1 mice reconstituted with normal syngeneic bone marrow (ATxBM). Thymocytes from BAF1 mice early after the induction of a GVH reaction (days 10-12) were as effective as normal thymocytes in reconstituting TH and mitogen responses. Thymocytes from BAF1 mice 40 or more days after the induction of a GVH reaction did not reconstitute either the TH function or PHA and Con A responses in ATxBM mice. The inability to reconstitute ATxBM mice was not due to the presence of suppressor cells contained in the thymocyte inoculum. It is proposed that GVH-induced thymic epithelial cell injury blocks or arrests normal T cell differentiation, resulting in a population of thymocytes that lack the potential to become competent T helper cells or mitogen-responsive cells when transferred into ATxBM mice. This thymic functional defect results in a permanent TH immunodeficiency in mice experiencing a chronic GVH reaction.