Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones

• Published in: The Journal of immunology (1950) Vol. 141; no. 7; pp. 2216 - 2220
• Main Authors: Gaspari, AA, Jenkins, MK, Katz, SI
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01-10-1988; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antibodies, Monoclonal; Binding, Competitive; Biological and medical sciences; Cell interactions; Clone Cells - immunology; Epidermis - cytology; Epidermis - immunology; Epitopes - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Haptens - immunology; Histocompatibility Antigens Class II - immunology; Immune Tolerance; Immunobiology; Interferon-gamma - administration & dosage; Keratins; Langerhans Cells - immunology; Lymphocyte Activation; Mice; Mice, Inbred C3H; Recombinant Proteins - administration & dosage; T-Lymphocytes, Helper-Inducer - immunology; Trinitrobenzenes - immunology; Cell function; Induction; Major histocompatibility system; Rodentia; Class II histocompatibility antigen; Non response; Ia-System; In vitro; Hapten; Antigen; Vertebrata; Specificity; Mammalia; Cell line; Mouse; Keratinocyte; T»-Lymphocyte; Clone
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.141.7.2216

Previous studies of Ia+ keratinocytes (KC) indicated that they functioned poorly or not at all when utilized as accessory cells for T cell activation. When Ia+ KC were modified with trinitrobenzene sulfonic acid, these cells did not induce a proliferative response in the TNP-specific, 1-Ek-restricted Th1 clone SE-4 (less than 5% of control). Analysis of supernatants generated from SE-4 cells incubated with these non-stimulatory accessory cells revealed low levels of IL-3 and IFN-gamma, but an absence of IL-2, when compared with supernatants generated from SE-4 cells stimulated with TNP-modified cultured Langerhans' cells that contain high levels of all of these lymphokines. Incubation of SE-4 cells with TNP-modified Ia+, but not Ia- KC or FITC-modified Ia+ KC, resulted in unresponsiveness to subsequent stimulation with TNP-modified functional accessory cells. Blocking studies with anti-class II MHC mAb revealed that the induction of unresponsiveness by hapten-modified Ia+ KC was restricted to the I-Ek molecule. Thus, the Ag and MHC specificities of unresponsiveness induced by TNP-modified Ia+ KC were identical to those observed for the proliferation of this clone in response to TNP-modified functional accessory cells. These data indicate the existence of a naturally occurring population of Ia+ cells that, after hapten-modification, induce an unresponsive state instead of proliferation of T cells.