The host response in graft versus host disease. I. Radiosensitive T cells of host origin inhibit parental anti-F1 cytotoxicity in murine chronic graft versus host disease.

Murine graft versus host (GVH) disease takes two forms depending on the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We now report that this marked disparity in disease expression results from a radio-sensitive host mechanism which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing chronic GVH disease. Cellular analysis revealed that protection in chronic GVH disease is mediated by a phenotypically complex system of genetically unrestricted radiosensitive T cells of F1 origin. These cells fail to functionally emerge in mice undergoing acute lethal GVH disease.

Modulation of murine in vitro immune response by verapamil (V).

Functionally distinct lymphocyte subsets differ with regard to necessary activation signals. In selected circumstances lymphocyte activation has been shown to be critically dependent upon transcellular calcium influx. Whether calcium plays a central role in the activation of all lymphocytes remains to be determined. The effect of the calcium channel blocker verapamil on the induction of murine cytotoxic T lymphocytes (CTL), suppressor cells, T helper cells, and B cells was investigated. Verapamil (V) was found to inhibit the induction of cytotoxic effector cells. V acted primarily on the afferent limb of this immune response, was synergistic with cyclosporin A (CsA), and its effects could be largely reversed by the addition of exogenous helper factors. V also inhibited B cell proliferation in response to anti-mouse IgM in the presence of 2-mercaptoethanol, but in the absence of cognate or non-cognate T cell help. In contrast to this, V did not inhibit the activation of cells capable of inducing B cell proliferation nor did it inhibit the induction of suppressor cells. The selective suppression of V is discussed in terms of activation requirements of CTL, suppressor cells and helper cell subsets.