Uveitogenicity is associated with a Th1-like lymphokine profile: cytokine-dependent modulation of early and committed effector T cells in experimental autoimmune uveitis.
This study addresses the nature of the pathogenic effector T cell in experimental autoimmune uveoretinitis and the effect of different cytokines on these cells in vitro. Lymph node cells of B10.RIII mice immunized with the uveitogenic peptide 161-180 of interphotoreceptor retinoid binding protein were cultured with the peptide with or without IL-12, IL-4, or anti-IL-4. An antigen-specific T cell line was subsequently derived from these cells. Primary cultures of immune lymph node cells stimulated with the peptide proliferated and produced IL-2 and some IL-4, but no IFN-gamma. The addition of recombinant IL-12 resulted in abundant production of IFN-gamma, which was blocked by the addition of IL-4 and was enhanced by anti-IL-4. Only those cultures that produced IFN-gamma in vitro were uveitogenic in vivo. A long-term uveitogenic T cell line, initially derived in the presence of IL-12, produced IFN-gamma and IL-2, but not IL-4, and was CD4+ (Th1-like). Antigen-specific proliferation and IFN-gamma production of the line were enhanced by exogenous IL-4, TGF-beta, IL-2, IL-6, IL-7, and IL-9 and were inhibited by IL-10 and TNF-alpha. Our results provide support for the hypothesis that the uveitogenic effector T cell has a Th1-like phenotype. Furthermore, the data suggest that the effects of the cytokine milieu on fully differentiated Th1 effectors may differ considerably from their effects on less mature stages of antigen-specific T cells.
Xu
H
H
Laboratory of Immunology, NEI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rizzo
L V
LV
Silver
P B
PB
Caspi
R R
RR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D005136:Eye Proteins; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012173:Retinitis / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014605:Uveitis / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D005136:Eye Proteins; D007371:Interferon-gamma; D018664:Interleukin-12; D007376:Interleukin-2; D015847:Interleukin-4; D008222:Lymphokines; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial