A dose effect of IL-7 on thymocyte development.
Blood
; 104(5): 1419-27, 2004 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-15155461
ABSTRACT
To study interleukin-7 (IL-7) in early thymocyte development, we generated mice transgenic (Tg) for the IL-7 gene under control of the lck proximal promoter. Founder line TgA, with the lowest level of IL-7 overexpression, showed enhanced alphabeta T-cell development. In contrast, in the highest overexpressing founder line, TgB, alphabeta T-cell development was disturbed with a block at the earliest intrathymic precursor stage. This was due to decreased progenitor proliferation as assessed by Ki-67 staining and in vivo bromodeoxyuridine (BrdU) incorporation. Bcl-2 was up-regulated in T-cell-committed progenitors in all Tg lines, and accounted for greater numbers of double positive (DP), CD4 single positive (SP), and CD8SP thymocytes in TgA mice where, in contrast to TgB mice, thymocyte progenitor proliferation was normal. Mixed marrow chimeras using TgB(+) and congenic mice as donors, and experiments using anti-IL-7 monoclonal antibody (MAb) in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype. In conclusion, at low Tg overexpression, IL-7 enhanced alphabeta T-cell development by increasing thymocyte progenitor survival, while at high overexpression IL-7 reduces their proliferation, inducing a dramatic block in DP production. These results show for the first time in vivo a dose effect of IL-7 on alphabeta T-cell development and have implications for IL-7 in the clinical setting.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Interleucina-7
/
Regulação da Expressão Gênica no Desenvolvimento
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos