Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins

Fang Huang, Yasuyuki Kitaura, Ihn Kyung Jang, Mayumi Naramura, Hemanta H H. Kole, Liping Liu, Haiyan Qin, Mark S S. Schlissel, Hua Gu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Casitas B cell lymphoma (Cbl) proteins are negative regulators for T cell antigen receptor (TCR) signaling. Their role in thymocyte development remains unclear. Here we show that simultaneous inactivation of c-Cbl and Cbl-b in thymocytes enhanced thymic negative selection and altered the ratio of CD4+ and CD8+ T cells. Strikingly, the mutant thymocytes developed into CD4+- and CD8+-lineage T cells independent of the major histocompatibility complex (MHC), indicating that the CD4+- and CD8+-lineage development programs are constitutively active in the absence of c-Cbl and Cbl-b. The mutant double-positive (DP) thymocytes exhibited spontaneous hyperactivation of nuclear factor-kappa B (NF-κB). Additionally, they failed to downregulate the pre-TCR and pre-TCR signaling. Thus, our data indicate that Cbl proteins play a critical role in establishing the MHC-dependent CD4+ and CD8+ T cell development programs. They likely do so by suppressing MHC-independent NF-κB activation, possibly through downmodulating pre-TCR signaling in DP thymocytes.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalImmunity
Volume25
Issue number4
DOIs
StatePublished - Oct 1 2006

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B-Cell Lymphoma
Thymocytes
T-Cell Antigen Receptor
T-Lymphocytes
Major Histocompatibility Complex
Proteins
NF-kappa B
CD4-CD8 Ratio
Down-Regulation

Keywords

  • CELLIMMUNO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins. / Huang, Fang; Kitaura, Yasuyuki; Jang, Ihn Kyung; Naramura, Mayumi; Kole, Hemanta H H.; Liu, Liping; Qin, Haiyan; Schlissel, Mark S S.; Gu, Hua.

In: Immunity, Vol. 25, No. 4, 01.10.2006, p. 571-581.

Research output: Contribution to journalArticle

Huang, F, Kitaura, Y, Jang, IK, Naramura, M, Kole, HHH, Liu, L, Qin, H, Schlissel, MSS & Gu, H 2006, 'Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins', Immunity, vol. 25, no. 4, pp. 571-581. https://doi.org/10.1016/j.immuni.2006.08.021
Huang, Fang ; Kitaura, Yasuyuki ; Jang, Ihn Kyung ; Naramura, Mayumi ; Kole, Hemanta H H. ; Liu, Liping ; Qin, Haiyan ; Schlissel, Mark S S. ; Gu, Hua. / Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins. In: Immunity. 2006 ; Vol. 25, No. 4. pp. 571-581.
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