Alloantigen presentation by individual clones of mouse splenic macrophages. Selective expression of IL-1 alpha in response to CD8+ T cell-derived IFN-gamma defines the alloantigen-presenting phenotype.

Approximately one-third of mouse splenic macrophage (M theta) progenitors yield progeny that constitutively present MHC class I alloantigen to naive T cells, a response that is restricted to CD8+ T cells and is elicited in a CD4+ Th cell-independent manner. In addition, both the alloantigen-presenting (alloAP+) and nonpresenting (alloAP-) M theta subsets constitutively express similar levels of MHC class I molecules, and their alloAP phenotypes are unaffected by IFN-gamma, which enhances the expression of both class I and II MHC molecules. We therefore postulated the restricted expression of costimulator molecules to account for the alloAP+ phenotype. Using cytokine-specific antibodies, recombinant mouse cytokines, and polymerase chain reaction analyses (to detect specific cytokine mRNA transcripts), we identified the putative costimulators as IL-1 alpha, IL-6, and TNF-alpha. TNF-alpha transcripts were present in both the alloAP+ and alloAP- M theta subsets, but IL-1 alpha and IL-6 were not constitutively expressed by the alloAP+ subset of M theta; rather, they were induced by IFN-gamma, which was released from naive CD8+ T cells only during coculture with alloAP+ M theta. Although IFN-gamma induced IL-6 gene transcription in both alloAP+ and alloAP- M theta subsets, it induced IL-1 alpha transcripts only in the alloAP+ subset. Finally, CD8+ T cells exposed to alloAP- M theta were unresponsive when subsequently cultured with alloAP+ M theta. We conclude that the ability of some M theta to elicit IFN-gamma from CD8+ T cells and to respond to this cytokine by producing IL-1 alpha defines the alloAP phenotype of the cell population, and that alloAP- M theta induce a state of alloantigen-specific tolerance in naive CD8+ T cells.