Large functional repertoire of regulatory T-cell suppressible autoimmune T cells in scurfy mice.
Scurfy mice which lacks functional Foxp3 transcription factor and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, spontaneously develop autoimmune responses against skin, lung, liver and tail. However, many organs/tissues are spared from autoimmune attack. Here, we demonstrate that scurfy mice contain dormant autoimmune T cells that induced new diseases such as sialoadenitis, dacryoadenitis, pancreatitis, gastritis, intestinal inflammation, colitis, and myositis in RAG-1 KO mice. Inflammation in as many as 12 organs/tissues was consistently induced in individual recipients with scurfy lymph node cells containing as few as 1.25 x 10(6) CD4(+) T cells. Moreover, transfer of the multiple organ autoimmune diseases could be suppressed by as little as 0.5 x 10(6) CD4(+)CD25(+) Treg cells, mediated by inhibiting autoimmune T-cell expansion. Our study provides evidence for the presence of a large repertoire of autoimmune lymphocytes against various organs/tissues in scurfy mice as well as Treg cells in B6 mice capable of suppressing the expansion of these autoimmune lymphocytes. Various conditions that control the expression of autoimmune T cells are discussed.
Sharma
Rahul
R
Department of Medicine, Division of Rheumatology and Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Jarjour
Wael N
WN
Zheng
Lingjie
L
Gaskin
Felicia
F
Fu
Shu Man
SM
Ju
Shyr-Te
ST
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D018398:Homeodomain Proteins / Q000235:genetics; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D053645:Interleukin-2 Receptor alpha Subunit; C064658:RAG-1 protein