The Inability of Educated T Cells to Mediate DTH Responses in T Cell - depleted Syngeneic Mice

Immune responses to the synthetic polypeptide poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) [(T,G)-A--L] 1 (1), such as humoral responses (2), delayed-type hypersensitivity responses (DTH) (3), and antigen-dependent T-cell proliferation, (4) are regulated by genes that are located in the major histocompatibility complex of the mouse (H-2). Thus, mice possessing the H-2 b haplotype are responders and mice of the H-2 a'ax'k'8 haplotypes are nonresponders. In a previous study (3), we have demonstrated the existence of two types of nonresponder mouse strains: (a) H-2 a and H-2 k haplotypes; educated T cells of these strains could mediate D T H responses to (T,G)A--L in the appropriate (responder × nonresponder)F1 mice but not in syngeneic recipients, and (b) H-2 t and H-2 s haplotypes; T cells of these strains could not be activated to mediate DTH responses in any recipient. These studies suggested that the defect in DTH responses to (T,G)-A--L in H-2 ~ and H-2 k mice is not expressed on their T cells or on their antigen-presenting cells in the activation phase. In this study we have analyzed the efferent phase of the D TH response to (T,G)A--L to identify the cell type which expresses the genetic defect. Here we have demonstrated that, for efficient D TH responses, T-T-cell collaboration is required. In addition, we have located the genetic defect of nonresponder (H-2 k and H-2 ~) mice in the efferent stage of the immune process, namely, in a second T-cell population that is needed for the manifestation of specific D T H reactions to (T,G)-A--L.