Differential Expression of Major Histocompatibility Complex Class II Genes on Murine Macrophages Associated with T Cell Cytokine Profile and Protective/Suppressive Effects

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-06, Vol.95 (12), p.6936-6940
• Main Authors: Baumgart, Martin, Moos, Verena, Schuhbauer, Diana, Muller, Brigitte
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Antibodies; Antigens; B lymphocytes; Biological Sciences; Cell Line; Cells; Cytokines; Cytokines - immunology; Disease; Gene Expression Regulation - immunology; Genes; Haplotypes; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Immunity (Disease); Lymphocyte Activation; Macrophage Activation; Macrophages; Macrophages - immunology; MHC class II genes; Mice; Molecules; Rodents; T lymphocytes; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.12.6936

Protective/suppressive major histocompatibility complex (MHC) class II alleles have been identified in humans and mice where they exert a disease-protective and immunosuppressive effect. Various modes of action have been proposed, among them differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To test this possibility, the expression of H-2 molecules from the four haplotypes H-2b, H-2d, H-2k, and H-2qwas determined on bone marrow-derived macrophages (BMDMs) and splenic B cells. The I-Aband I-Ekmolecules, both well characterized as protective/suppressive, are expressed at a high level on almost all CD11b+BMDMs for 5-8 days, after which expression slowly declines. In contrast, I-Ad, I-Ak, and I-Aqexpression is lower, peaks over a shorter period, and declines more rapidly. No differential expression could be detected on B cells. In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay with BMDMs as antigen-presenting cells. The results indicate that macrophages of the protective/suppressive haplotypes express MHC class II molecules at a high level and exert Th1 bias, whereas low-level expression favors a Th2 response. We suggest that the extent of expression of the class II gene gates the back signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic nonexon segments of MHC class II genes may play a role in determining disease susceptibility in humans and mice.