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Lymphopenia-Induced Proliferation Is a Potent Activator for CD4⁺ T Cell-Mediated Autoimmune Disease in the Retina¹

Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455

To study retinal immunity in a defined system, a CD4⁺ TCR transgenic mouse line (βgalTCR) specific for β-galactosidase (βgal) was created and used with transgenic mice that expressed βgal in retinal photoreceptor cells (arrβgal mice). Adoptive transfer of resting βgalTCR T cells, whether naive or Ag-experienced, into arrβgal mice did not induce retinal autoimmune disease (experimental autoimmune uveoretinitis, EAU) and gave no evidence of Ag recognition. Generation of βgalTCR T cells in arrβgal mice by use of bone marrow grafts, or double-transgenic mice, also gave no retinal disease or signs of Ag recognition. Arrβgal mice were also resistant to EAU induction by adoptive transfer of in vitro-activated βgalTCR T cells, even though the T cells were pathogenic if the βgal was expressed elsewhere. In vitro manipulations to increase T cell pathogenicity before transfer did not result in EAU. The only strategy that induced a high frequency of severe EAU was transfer of naive, CD25-depleted, βgalTCR T cells into lymphopenic arrβgal recipients, implicating regulatory T cells in the T cell inoculum, as well as in the recipients, in the resistance to EAU. Surprisingly, activation of the CD25-depleted βgalTCR T cells before transfer into the lymphopenic recipients reduced EAU. Taken together, the results suggest that endogenous regulatory mechanisms, as well as peripheral induction of regulatory T cells, play a role in the protection from EAU.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grants EY011542 and EY016376; Research to Prevent Blindness, The Anna Heilmaier Foundation (St. Paul, MN), and the Minnesota Lions and Lionesses Clubs.

² Address correspondence and reprint requests to Dr. Scott W. McPherson, Department of Ophthalmology, University of Minnesota, 2001 6th Street SE, Minneapolis, MN 55455-3007. E-mail address: mcphe003{at}umn.edu

³ Abbreviations used in this paper: EAU, experimental autoimmune uveoretinitis; arrβgal, photoreceptor expression of βgal; BM, bone marrow; βgal, Escherichia coli β-galactosidase; βgalTCR, βgal-specific TCR Tg T cells; GFAPβgal, astrocyte expression of βgal; HEL, hen egg lysozyme; LIP, lymphopenia-induced proliferation; LN, lymph node; MBP, myelin basic protein; PTx, pertussis toxin; Tg, transgenic; Treg, regulatory T cell.

This article has been cited by other articles:

				D. S. Gregerson, N. D. Heuss, U. Lehmann, and S. W. McPherson Peripheral Induction of Tolerance by Retinal Antigen Expression J. Immunol., July 15, 2009; 183(2): 814 - 822. [Abstract] [Full Text] [PDF]