Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 202, Issue 6, Pages 771-781Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041033
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Funding
- NCI NIH HHS [P30 CA44579, P30 CA044579] Funding Source: Medline
- NIAID NIH HHS [R01 AI041236, AI-41236, R01 AI051420, R21 AI051420, AI-51420] Funding Source: Medline
- NIAMS NIH HHS [P50 AR045222, AR45222] Funding Source: Medline
- NICHD NIH HHS [HD-44415, U01 HD044415] Funding Source: Medline
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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.
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