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PA Dullforce, GW Seitz, KL Garman, SM Crespo, SR Planck, DC Parker, JT Rosenbaum; Resting, Rather Than Activated, T Cells Preferentially Infiltrate the Murine Iris Upon Local Antigen Challenge . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1552.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Using ovalbumin (OVA) specific transgenic T cells, we sought to investigate the role of T cells in a murine model of anterior uveitis. Methods: T cells isolated from DO11.10 transgenic mice were either highly enriched for CD4+ cells (resting cells) or incubated in vitro with ovalbumin323-339 peptide for four days resulting in the generation of DO11.10 blasts (activated cells). Both resting and activated cells were labeled with the fluorescent dye, CFSE, and transferred into syngeneic BALB/c host mice. One to seven days afterwards, the anterior chambers of the hosts were injected with 150µg of ovalbumin (OVA) or human serum albumin (HSA). The location of labeled DO11.10 T cells in the anterior segment at 6, 12, 24, 48 and 72 hours was monitored by intravital microscopy on anesthetized animals. The proliferation of the DO11.10 cells in the draining mandibular and superficial cervical lymph nodes was detected by flow cytometry. Results: In previous work we demonstrated that in vitro activated, CFSE-labeled DO11.10 cells localize preferentially to the ciliary body and limbus during the time course of a mild uveitis induced by challenge with OVA in the anterior chamber. Few activated DO11.10 cells, however, are found in the iris, even at 48 hours when inflammation peaks. In contrast CD4+ cells derived directly from normal DO11.10 mice accumulate in the iris as well as the ciliary body and limbus upon OVA challenge. Fewer transferred cells accumulate in the anterior segment of eyes challenged with HSA. CFSE-labeled resting CD4+ cells from BALB/c mice do not accumulate in the OVA treated eyes over the time course of the uveitis. Proliferation of DO11.10 cells in the lymph nodes is not detected until 48 hours, implying that the steady accumulation of CFSE-labeled cells at 6, 24 and 48 hours comprised resting cells. Whether the cells proliferate in the anterior segment is uncertain, but confocal images indicate interaction with MHC class II+ dendritiform cells. Conclusion: Resting, but not activated, T cells can infiltrate murine iris during the course of OVA-induced anterior uveitis. Whether these resting T cells have never seen antigen or are a memory cell population warrants investigation.
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