Induction of ocular inflammation by T-helper lymphocytes type 2.
OBJECTIVE
Sight-damaging ocular inflammation is often mediated by T-helper (Th) lymphocytes. The population of Th cells is divided into two major subsets, designated Th1 and Th2, that differ by their cytokine production and biological activities. In the present study, the capacity of Th1 and Th2 cells to induce ocular inflammation was examined.


METHODS
Ocular inflammation was induced in transgenic (Tg) mice that express hen egg lysozyme (HEL) in their lens, by adoptively transferring Th cells that transgenically express HEL-specific receptor. Th1 and Th2 populations were polarized in vitro, and their selective cytokine production was determined by conventional methods. Levels of ocular inflammation were monitored by conventional histologic methods. Infiltrating cells were collected from sections of inflamed eyes by microdissection, and their cytokine production was examined by RT-PCR.


RESULTS
Th1 cells were highly immunopathogenic, producing disease in naive recipients at numbers as low as 0.12 x 10(6), whereas Th2 cells were inactive in these recipients, even at 30 x 10(6). Th2 cells, however, produced inflammation when transferred into sublethally irradiated recipients. Distinctive histopathologic changes characterized ocular inflammation induced by the two types of Th cells. Cytokine analysis of infiltrating cells in recipient mouse eyes, as well as of splenocytes of these mice demonstrated that the transferred cells retained their type specificity. Coinjecting Th2 and Th1 cells did not alleviate the ocular disease in naive recipients and even exacerbated the immunopathogenic process in irradiated recipients.


CONCLUSIONS
Th2 cells are capable of inducing ocular inflammation, but only in immunodeficient mice, and are profoundly inferior to Th1 cells in their immunopathogenic capacity.
Kim
Stephen J
SJ
Laboratory of Immunology, Laboratory of Molecular and Developmental Biology, National Eye Institute/NIH, 10 Center Drive, Room 10N112, Bethesda, MD 20892-1857, USA.
Zhang
Meifen
M
Vistica
Barbara P
BP
Chan
Chi-Chao
CC
Shen
De-Fen
DF
Wawrousek
Eric F
EF
Gery
Igal
I
D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D007908:Lens, Crystalline / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014605:Uveitis / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; C421864:hen egg lysozyme; D009113:Muramidase