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A correction to this article has been published: Samy et al., J. Exp. Med. 202 (8) 1153
Published 19 September 2005. doi:10.1084/jem.20041033
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 6, 771-781
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ARTICLE

 Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node

Eileen T. Samy1,2, Lucy A. Parker1,2, Colin P. Sharp1, and Kenneth S.K. Tung1,2

1 Department of Pathology, University of Virginia, Charlottesville, VA 22908
2 Department of Microbiology, University of Virginia, Charlottesville, VA 22908

CORRESPONDENCE Kenneth S.K. Tung: kst7k{at}virginia.edu

This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-{gamma} production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.

Abbreviations used: AOD, autoimmune ovarian disease; BrdU, bromodeoxyuridine; CFSE, 5,6-carboxyfluorescein diacetate-succinimidyl ester; d3tx, day 3 thymectomy; EAE, experimental allergic encephalomyelitis; nOX, neonatal ovariectomy; PLP, proteolipid protein; T reg, CD4+CD25+ regulatory T cell.


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