Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones.
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.
Gaspari
A A
AA
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892.
Jenkins
M K
MK
Katz
S I
SI
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002999:Clone Cells / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000008:administration & dosage; D007633:Keratins; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000008:administration & dosage; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D014301:Trinitrobenzenes; D007633:Keratins; D007371:Interferon-gamma