Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice.
Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune disease induced by immunization with uveitogenic retinal antigens, or by the adoptive transfer of uveitogenic T-cells of the Th-1-like phenotype. We have previously shown that IFN-gamma-deficient mice (GKO) on the C57BL/6 background are equally susceptible to interphotoreceptor retinoid binding protein (IRBP)-induced EAU as the wild type (WT). In the present study, we evaluated EAU induction in GKO mice by the newly described H-2(b)epitope contained in residues 1-20 of human IRBP, and compared it to the response to the whole IRBP molecule. Similarly to previous observations with IRBP-induced EAU, delayed type hypersensitivity (DTH) and lymphocyte proliferation responses were elevated in GKO mice, as was production of IL-5 and TNF-alpha. However, unlike the responses induced by whole IRBP, there was no detectable IL-10 production to the peptide. Histopathology on day 21 after immunization, revealed that both GKO and WT mice developed retinal lesions, including damage to the photoreceptor cell layer, vasculitis and inflammatory cellular infiltration, but disease scores were significantly higher in GKO, and retinal detachment was observed only in GKO mice. In contrast to the wild type, the cellular infiltrate in eyes of GKO mice contained a prominent component of eosinophils, although of lower proportion in peptide-induced than in IRBP-induced EAU. We conclude that the cytokine and inflammatory responses to human peptide 1-20 differ perceptibly from the responses to whole bovine IRBP, and may explain the elevated EAU scores of GKO mice compared to wild type.
Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892, USA.
D
D
Avichezer
C C
CC
Chan
P B
PB
Silver
B
B
Wiggert
R R
RR
Caspi
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D002455:Cell Division; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency*; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D014605:Uveitis / Q000209:etiology / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D012177:Retinol-Binding Proteins; D007371:Interferon-gamma