Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia

Natasha J. Hill, Aleksandr B. Stotland, Nora E. Sarvetnick

Research output: Contribution to journalArticlepeer-review


IL-4 is protective against Type 1 diabetes in the NOD mouse. IL-4 promotes T cell survival in vitro, but little is known about the effect of IL-4 on clonal expansion in vivo. Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. The accumulation of proliferating cells induced by IL-4 in a lymphopenic host is inhibited incrementally by increasing the number of bystander cells and is prevented by cell numbers well below that of unmanipulated NOD mice. The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. These results suggest that IL-4-mediated protection against autoimmunity and diabetes may be outweighed during immunodeficiency by a pathogenic, IL-4-induced expansion of autoreactive T cells.

Original languageEnglish (US)
Pages (from-to)757-765
Number of pages9
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Mar 1 2007
Externally publishedYes


  • Autoimmunity
  • Cytokine
  • Diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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