Genetic Restrictions of Suppressor Cell Interactions

The complex regulatory interactions among T lymphocytes initiating, amplifying, and suppressing various effector-immune reactions have recently become the subject of intense investigation. We recently reported on a T cell participating in suppressing the delayed-type hypersensitivity (DTH) 1 response to the haptenic determinant 4hydroxy-3-nitrophenyl acetyl (NP) (1). We now report on a second population of suppressor T cells capable of modulating the effector phase of the NP-specific DTH response. NP derivatized syngeneic spleen cells given intravenously induce a population of T lymphocytes that, when administered to animals before sensitization with NP conjugated to bovine gamma globulin (BGG) (NP-BGG), would suppress NP-specific DTH responses elicited with NP conjugated to bovine serum albumin (BSA) (NP-BSA), a heterologous carrier. The fine specificity of these inducer-phase suppressor cells was similar to that of anti-NP antibodies. Thus, these inducer-phase suppressor cells adhered to NP-coated dishes. In addition, in strains of mice bearing the Igh-1 b allotype, the primary anti-NP antibody has a higher affinity for the 5-iodo derivative of NP (NIP) than the original immunizing hapten (2). This property, termed heteroclicity, was found to be demonstrable in the population of NP suppressor cells, i.e., NP-induced suppressor T cells would suppress specifically NIP-BGG-primed, NIP-specific DTH responses in the appropriate strains. The genetic mapping of this particular reactivity demonstrated that the Igh-V gene responsible for heteroclitic idiotypic antibody was closely linked to the gene controlling the NP-induced suppressor cell specificity. In addition, NP-induced suppressor T cells of Igh-1 b origin were specifically lysed by treatment with a guinea pig anti-NP b idiotype and complement, again demonstrating the expression of Igh-V-gene products in NP-specific suppressor T lymphocytes. In our previous experiments, the NP-specific suppressor T cells were adoptively transferred at the time of immunization and were, therefore, operationally considered afferent suppressor T cells.