Inhibitory Effect of Isoantibody on in vivo Sensitization and on the in vitroCytotoxic Action of Immune Lymphocytes

Abstract

KALISS was able to show that the enhancement of tumour grafts in allogeneic recipients is mediated by antibody¹. Three alternative mechanisms by which antibodies might exert their effect have been postulated by Billingham et al.²: (1) an afferent inhibition in which antibody combined with allogeneic cells prevents antigeneic determinants from reaching immunologically competent cells; (2) a central inhibition in which antibody, by direct action on lymphoid cells, prevents their sensitization; (3) an efferent inhibition in which antibody reacting with target cells protects against the cytotoxic action of immune lymphoid cells which are competing for the same antigenic receptors. Both the afferent and the central mechanisms would affect sensitization of lymphoid cells, thought to be the most important mediators of homograft rejection. Brent and Medawar³ demonstrated that extracts of antigenic tissue injected into recipients treated with antiserum did not provide immunization against a subsequent skin graft. Snell et al.⁴ showed that lymphoid cells from tumour allograft recipients which had been treated with antiserum were less efficient in inhibiting tumour growth than lymphoid cells from untreated recipients. Passive immunization is also known, however, to inhibit the synthesis of antibodies^4–6, and experiments involving transfer of immunologically competent cells cannot critically distinguish between cellular and humoral immunity. We have therefore analysed the effect of passive immunization on “cell bound immunity” using in vitro methods.