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.
McCormack
J M
JM
Department of Immunology, St. Jude Children's Research Hospital, Memphis TN 38105.
Askew
D
D
Walker
W S
WS
D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D007519:Isoantigens / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016827:CD8 Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D007519:Isoantigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma