IMMUNOLOGICAL STUDIES OF T-CELL RECEPTORS I. Specifically Induced Resistance to Graft-Versus-Host Disease in Rats Mediated by Host T-Cell Immunity to Alloreactive Parental T Cells* BY DONALD BELLGRAU AND DARCY

Systemic graft-versus-host (GVH) ~ disease arising in F~ animals injected with thymus-derived (T) lymphocytes of parental origin is a complex phenomenon (1). F~ animals express the transplantation antigens of both parents codominantly and it is generally assumed that they are unable to reject gral~ of immunocompetent parental lymphoid cells; as a consequence, they are susceptible to GVH disease. Normal adult F~ animals are comparatively resistant to GVH disease, the infusion of large numbers of parental cells being required to elicit GVH symptoms (2). In contrast, F~ hosts first given sublethal whole body irradiation are susceptible to much lower dosages of parental cells (2-5). There are several possible explanations that might be offered to account for the relative resistance of intact FI animals to GVH disease compared to irradiated recipients. It may reflect, for example, the ability of the host to develop an immune response against receptors present on donor parental strain T lymphocyte subpopulations specific for host antigens (6). For reasons of self-tolerance these receptors are considered to be lacking in the host and therefore they could be immunogenic. Recent studies (7) supporting this argument have demonstrated that a state of specific resistance to local GVH reactions can be induced in F1 rats by prior inoculation with subclinical doses of parental strain T cells. After immunization with lymphocytes from one parental strain (A), A/B FI animals no longer display the expected degree of lymph node enlargement in popliteal lymph node assays when they are subsequently injected with lymphocytes of the same parental strain. This resistance to local GVH reactions is specific for the immunizing parental strain (A), since cells from the other strain parent (B) continue to cause enlarged nodes. Furthermore, it depends on the presence in the immunizing strain A lymphocyte population of T cells with competence for strain B alloantigens; lymphocytes depleted of T cells, or T cells depeleted of