Tgf-beta inhibits activation and uveitogenicity of primary but not of fully polarized retinal antigen-specific memory-effector T cells.
OBJECTIVE
TGF-beta exerts suppressive effects on immunity, but its potential applications in therapy of ocular autoimmunity have not been widely explored. In the present study, the effects of TGF-beta on uveitogenic T cells were examined.


METHODS
The effects of TGF-beta on newly primed cells from mice given a uveitogenic regimen of interphotoreceptor retinoid-binding protein (IRBP) were compared with the effects on fully polarized Th1 cells from a long-term uveitogenic T-cell line. The parameters measured were T-cell proliferation, IFN-gamma production, induction of IL-12R expression, triggering of pathogenicity, and expression of costimulatory molecules on antigen-presenting cells (APCs) during in vitro exposure to antigen.


RESULTS
TGF-beta suppressed B7.1 expression on APCs in cultures of lymph node cells from immunized mice. It also suppressed T-cell proliferation, IFN-gamma production, IL-12 receptor accumulation, and the IL-12-promoted acquisition of uveitogenic function. In contrast, the polarized Th1 cells were either resistant to suppression or were enhanced by TGF-beta.


CONCLUSIONS
The results suggest that TGF-beta suppresses acquisition of effector functions by autopathogenic T cells, in part by interfering with their response to IL-12 through downregulation of IL-12R expression and in part through inhibition of APC function. The data suggest that although TGF-beta may effectively inhibit activation and recruitment of new T cells into the effector pool, it may be less effective in suppressing the reactivation of already polarized memory T cells that are less dependent on IL-12 and costimulation.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Hui
H
Xu
Phyllis B
PB
Silver
Teresa K
TK
Tarrant
Chi-Chao
CC
Chan
Rachel R
RR
Caspi
D000818:Animals; D000938:Antigen-Presenting Cells; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D018122:B7-1 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D018122:B7-1 Antigen; D005136:Eye Proteins; D007371:Interferon-gamma; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D012177:Retinol-Binding Proteins; D016212:Transforming Growth Factor beta; D000099214:Retinol-Binding Proteins, Interstitial