Specific Systemic Graft-Versus-Host Resistance: Failure to Induce in Adult F₁ Rats Tolerized at Birth to Anti-MHC Receptors on Parental T Cells

Abstract

The injection of mature thymus derived (T) lymphocytes into recipients unable to reject them often results in a complex syndrome referred to as graft-versus-host (GVH) disease (1). Originally A/B F₁ animals, where parents A and B are allogeneic and MHC incompatible, were thought to represent an ideal model system for the study of GVH as they lacked, due to codominant inheritance, the capacity to reject parental skin grafts and presumably parental T lymphocytes. However, Gowans (2) showed that in order to elicit GVH symptoms in F₁ rats, large doses of parental lymphocytes were required. Field et al. (3) later reported that F₁ rats challenged with nonlethal doses of parental lymphocytes were subsequently refractory to lethal doses. They concluded, following adoptive transfer experiments, that the radioinsensitivity of this GVH resistance (GVHR) was likely due to a humoral component. Ramseier and Lindenmann (4) proposed that F₁ animals might recognize as foreign and respond against the receptors on parental lymphocytes specific for F₁ alloantigens. This concept of F₁ anti-parental receptor immunity was strongly reinforced by McKearn (5) and Binz and Wigzell (6) who reported success in raising F₁ antibodies to parental T cell anti-MHC receptors.