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- Levéen, Per, et al.
(författare)
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TGF-{beta} type II receptor deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo.
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 106:13, s. 4234-4240
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Tidskriftsartikel (refereegranskat)abstract
- We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor β receptor II (TβRII). Using this approach, transforming growth factor β (TGF-β) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with TβRII-/- bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-β1-null mice. Previous in vitro studies have suggested multiple roles for TGF-β in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF-β signaling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF-β is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, TβRII-deficient CD8+ thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine (BrdU) incorporation in vivo. These results reinforce the importance of TGF-β as an immune regulator critical for T-cell function.
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