CUTANEOUS HYPERSENSITIVITY REACTIONS TO CELLULAR ISOANTIGENS IN RATS

Rats have been shown to be capable of displaying the various kinds of delayed cutaneous hypersensitivity reactions attributable to transplantation immunity previously described in guinea pigs, hamsters, rabbits, dogs, and man. The rat is unlike most other species in that much larger numbers of lymphoid cells are needed to incite these cutaneous reactions. With direct, transfer, or normal lymphocyte transfer reactions, the cutaneous responses were greater when donor and recipient differed at the Ag-B histocompatibility locus than when donor and recipient shared the same Ag-B alleles. An experiment was performed in which adult rats of a genetically defined backcross population, resulting from matings between DA and (DA x Lewis) F1 hybrid rats, were inoculated intradermally with lymph node cells from DA rats sensitized against tissues from Lewis-strain donors. Some of the R2 animals gave a biphasic transfer reaction with peak reactivities occurring first at 48 hr and recurring at 96–120 hr, while the others lacked this second component. Hemagglutination tests revealed that the R2 rats giving the biphasic response possessed the Ag-B,1 antigen, which is also present in Lewis rats, whereas rats which gave monophasic reactions were homozygous for the Ag-B,4 antigenic determinant which is present in the DA strain. This suggested that the recall flare at 96–120 hr reflects proliferative activity on the part of the inoculated cells confronted by the disparate Ag-B isoantigen in the host's dermis. Skin homografts from R1 animals bearing the Ag-B,1 antigen were uniformly rejected by DA hosts in 11 days or less, while grafts from backcross animals homozygous for the Ag-B,4 antigen usually lived longer, being rejected in 9 to 27 days. Evidence is also presented which suggests that specific isoantibodies may act synergistically with immune lymphocytes to bring about cutaneous inflammatory reactions in the rat.