Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node.
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.
Samy
Eileen T
ET
Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Parker
Lucy A
LA
Sharp
Colin P
CP
Tung
Kenneth S K
KS
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005260:Female; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010049:Ovarian Diseases / Q000276:immunology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D018984:Epitopes, T-Lymphocyte; D015375:Receptors, Interleukin-2