Abstract
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 language | English (US) |
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Pages (from-to) | 757-765 |
Number of pages | 9 |
Journal | Journal of Leukocyte Biology |
Volume | 81 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2007 |
Externally published | Yes |
Keywords
- Autoimmunity
- Cytokine
- Diabetes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology