Regulatory T cells and vasectomy

Claudia Rival, Karen Wheeler, Sarah Jeffrey, Hui Qiao, Brian Luu, Eric F. Tewalt, Victor H. Engelhard, Stephen Tardif, Daniel Hardy, Roxana del Rio, Cory Teuscher, Kenneth Tung

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

CD4+ CD25+ regulatory T cells (Tregs) strongly influence the early and late autoimmune responses to meiotic germ cell antigens (MGCA) and the gonadal immunopathology in vasectomized mice. This is supported by the published and recently acquired information presented here. Within 24. h of unilateral vasectomy (uni-vx) the ipsilateral epididymis undergoes epithelial cell apoptosis followed by necrosis, severe inflammation, and granuloma formation. Unexpectedly, vasectomy alone induced MGCA-specific tolerance. In contrast, uni-vx plus simultaneous Treg depletion resulted in MGCA-specific autoimmune response and bilateral autoimmune orchitis. Both tolerance and autoimmunity were strictly linked to the early epididymal injury. We now discovered that testicular autoimmunity in uni-vx mice did not occur when Treg depletion was delayed by one week. Remarkably, this delayed Treg depletion also prevented tolerance induction. Therefore, tolerance depends on a rapid de novo Treg response to MGCA exposed after vasectomy. Moreover, tolerance was blunted in mice genetically deficient in PD-1 ligand, suggesting the involvement of induced Treg. We conclude that pre-existing natural Treg prevents post-vasectomy autoimmunity, whereas vasectomy-induced Treg maintains post-vasectomy tolerance. We further discovered that vasectomized mice were still resistant to autoimmune orchitis induction for at least 12-16 months; thus, tolerance is long-lasting. Although significant sperm autoantibodies of low titers became detectable in uni-vx mice at 7 months, the antibody titers fluctuated over time, suggesting a dynamic "balance" between the autoimmune and tolerance states. Finally, we observed severe epididymal fibrosis and hypo-spermatogenesis at 12 months after uni-vx: findings of highly critical clinical significance.

Original languageEnglish (US)
Pages (from-to)66-75
Number of pages10
JournalJournal of Reproductive Immunology
Volume100
Issue number1
DOIs
StatePublished - Nov 2013
Externally publishedYes

Keywords

  • Autoimmune orchitis
  • Genetic control of autoimmunity
  • Post-vasectomy sequel
  • Regulatory T cells
  • Sperm autoantibodies
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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