TY - JOUR
T1 - CD28 disruption exacerbates inflammation in Tgf-β1-/- mice
T2 - In vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-β1
AU - Mamura, Mizuko
AU - Lee, Woon Kyu
AU - Sullivan, Timothy J.
AU - Felici, Angelina
AU - Sowers, Anastasia L.
AU - Allison, James P.
AU - Letterio, John J.
PY - 2004/6/15
Y1 - 2004/6/15
N2 - Tgf-β1-/- mice develop a progressive, lethal, Inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-β1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-β1-/- mice, and we link this increase in severity to a reduction in the number of CD4 +CD25+ regulatory T cells. CD4+CD25 + T cells develop normally in Tgf-β1-/-mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), αEβ7 integrin, and Foxp3. Adoptive transfer of Tgf-β1-/- splenocytes to Tgf-β1+/+/Rag2 -/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-β1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-β1-/- CD4 +CD25+ T cells from donor splenocytes. Cotransfer of Tgf-β1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25 +-depleted Tgf-β1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-β1+/+ CD4+CD25+ T cells. These data demonstrate that CD4 +CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-β1 (TGF-β1) expression and that autocrine TGF-β1 expression is not essential for these cells to suppress inflammation in vivo.
AB - Tgf-β1-/- mice develop a progressive, lethal, Inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-β1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-β1-/- mice, and we link this increase in severity to a reduction in the number of CD4 +CD25+ regulatory T cells. CD4+CD25 + T cells develop normally in Tgf-β1-/-mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), αEβ7 integrin, and Foxp3. Adoptive transfer of Tgf-β1-/- splenocytes to Tgf-β1+/+/Rag2 -/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-β1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-β1-/- CD4 +CD25+ T cells from donor splenocytes. Cotransfer of Tgf-β1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25 +-depleted Tgf-β1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-β1+/+ CD4+CD25+ T cells. These data demonstrate that CD4 +CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-β1 (TGF-β1) expression and that autocrine TGF-β1 expression is not essential for these cells to suppress inflammation in vivo.
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U2 - 10.1182/blood-2003-08-2897
DO - 10.1182/blood-2003-08-2897
M3 - Article
C2 - 15016653
AN - SCOPUS:2942627115
SN - 0006-4971
VL - 103
SP - 4594
EP - 4601
JO - Blood
JF - Blood
IS - 12
ER -