886 Alloantibody Production and Histoincom

Despite intensive investigation, the essential mechanisms of allograft rejection or tolerance have remained obscure. Although there is now no doubt that juvenile as well as adult individuals respond to foreign tissue grafts with production of serum antibodies against the alloantigens (isoantigens) of the donor, the possible roles of such antibodies in graft rejection continue to be controversial. Circulating antibodies against graft antigens are generally cytotoxic only for dissociated and especially lymphoid cells. Solid tissue transplants such as skin, kidney, or tumors are rarely vulnerable to serum antibodies alone. Indeed, such grafts often show prolonged survival or enhancement as a consequence of passive transfer of specific antiserum to the graft recipient. Much evidence suggests that specifically immune lymphocytes are the essential agents in the destruction of most types of aUografts (1). This conclusion follows in particular from the often repeated finding that lymphocytes from immunized animals will adoptively transfer immunity to normal animals, whereas even hyperimmune serum from comparable donors fails to do so. Allograft rejection then has many of the characteristics of cellular hypersensitivity of the delayedor tuberculintype. The details of how immune lymphocytes or their transformed descendants kill foreign target cells are still unknown. Perhaps a special class of cell-bound antibodies or even induced enzymes may be involved. The recent discovery of four or more major classes of circulating immunoglobulins, each with distinctive physico-chemical and biological properties as well as intraciass differences (2, 3), adds new dimensions to the possibility that certain typical antibodies may be associated with transplantation immunity. Thus the failure of whole hyperimmune serum to mediate allograft rejection passively could be attributable to opposing effects of different molecular species of antibodies. Recently we have found that only macroglobulin (i.e. 19S or IgM) alloantibodies are inducible in infant or juvenile mice, whereas older mice regularly produce 7S IgG aUoantibodies in addition to macroglobulins (4). Yet m~x4mal transplantation immunity of the adult type is inducible in neonates before even macrogiobulin aUohemaggiutinins are readily detectable under diverse tactics of immunization. How-