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Brinda Subbarayal, Antonio Di Zazzo, Susanne Eiglmeier, SANGMOK LEE, Sunil Chauhan, Reza Dana; Proinflammatory Th17 cells are more effective than Th1 cells in providing B cell help in dry eye disease.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4877.
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© ARVO (1962-2015); The Authors (2016-present)
T cell help is known to be fundamental for the induction and subsequent organization of germinal centers (GCs), resulting in the generation of memory B cells and long-lived plasma cells. However, it is not known whether Th17 cells can act as effective helper T cells in experimental dry eye disease (DED). The aim of this study was to determine whether Th17 cells function as helper cells for B cells in DED.
Dry eye was induced by exposing female C57BL/6 mice to desiccating stress (subcutaneous injection of scopolamine [0.5 mg/ 0.1 mL] 3 times a day, humidity < 15%, and airflow rate of 15L/min) for 3 weeks. To determine the kinetics of GC formation and isotype switched B cells, cervical lymph nodes were stained for GCs (B220+GL7+FAS+) and isotype switched (B220+IgD-IgM-) B cells on day 0, 7, 14, 21, and 28 using flow cytometry. On day 21, formation of GCs was analyzed by immunhistochemistcal staining of lymph node sections with anti-ki67-FITC and anti-IgM-APC antibodies. T cell-B cell coculture assays were performed to determine T cell help on B cells. The cells were activated with 1μg/ml of anti-CD3 and 1μg/ml of anti-IgM for 36hours before analyzing B cell proliferation using flow cytometry.
Germinal center B cell formation in the lymph nodes of DED mice peaked on day 21, whereas no GC formation was observed in naïve mice. T effector (Teff) cells from DED mice significantly enhanced B cell proliferation in a contact dependent manner. To determine whether Th1<br /> (IFN-γ+) or Th17 (IL-17+) cells provide major B cell help, IFN-γ or IL-17 depleted Teff (CD4+CD25-) cells were cocultured with B cells. Although both subsets effectively reduced B cell proliferation in vitro, Th17 cells were more effective than Th1 cells in helping B cell proliferation in DED mice.
Th17 cells are more effective than Th1 cells in inducing B cell proliferation in DED.
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