Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease.
Thymectomy of BALB/c mice on day 3 of life results in the development of autoimmune gastritis (AIG) due to the absence of CD4(+)CD25(+) regulatory T cells. However, depletion of CD4(+)CD25(+) T cells by treatment with anti-CD25 rarely resulted in AIG. Depletion was efficient, as transfer of splenocytes from depleted mice induced AIG in nu/nu mice. One explanation for this result is that CD4(+)CD25(-) T cells upon transfer to nude recipients undergo lymphopenia-induced proliferation, providing a signal for T cell activation. Cotransfer of CD25(+) T cells did not inhibit initial proliferation but did suppress AIG. Surprisingly, immunization with the AIG target Ag, H/K ATPase, in IFA failed to induce disease in normal animals but induced severe AIG in CD25-depleted mice. These results demonstrate that second signals (nonspecific proliferation, TCR activation, or inflammation) are needed for induction of autoimmunity in the absence of CD25(+) regulatory T cells.
McHugh
Rebecca S
RS
Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shevach
Ethan M
EM
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis*; D002455:Cell Division / Q000276:immunology; D005260:Female; D005756:Gastritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D017506:H(+)-K(+)-Exchanging ATPase / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007274:Injections, Intraperitoneal; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009928:Organ Specificity / Q000276:immunology; D011817:Rabbits; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D017506:H(+)-K(+)-Exchanging ATPase