Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia.
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.
Hill
Natasha J
NJ
The Scripps Research Institute, , IMM-23, La Jolla, CA 92037, USA.
Stotland
Aleksandr B
AB
Sarvetnick
Nora E
NE
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D015847:Interleukin-4