Requirement of calcineurin Aβ for the survival of naive T cells

Santhakumar Manicassamy, Sonal Gupta, Zhaofeng Huang, Jeffery D. Molkentin, Weirong Shang, Zuoming Sun

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Calcineurin (Cn) is a Ca2+/calmodulin-dependent phosphatase that dephosphorylates and activates NFAT, a transcription factor essential for T cell activation. T lymphocytes predominantly express the calcineurin Aβ (CnAβ) isoform, and the deletion of the CnAβ gene results in defective T cell proliferation and IL-2 production in response to TCR stimulation. In this study, we show that CnAβ enhances the spontaneous survival of naive T cells by maintaining high levels of Bcl-2, a critical homeostatic survival factor for naive T cells. T cells obtained from CnAβ-/- mice displayed accelerated spontaneous apoptosis. The observed apoptosis of the CnAβ-/- T cells was prevented by IL-7 and IL-15, two cytokines critical for the homeostatic survival of naive T cells. Furthermore, CD4 + or CD8+ single positive CnAβ-/- thymocytes also underwent accelerated apoptosis. However, no obvious difference in the apoptosis of CD4+CD8+ double positive thymocytes was observed between CnAβ-/-and wild-type mice, suggesting a specific function of CnA+ in the survival of single positive T cells. Bcl-2 levels were found to be significantly lower in CnAβ-/- T cells. Transgenic expression of Bcl-xL restored the survival of the CnAβ-/- T cells. Thus, in addition to its role in mediating TCR signals essential for T cell activation, CnAβ is also required for the homeostatic survival of naive T cells.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalJournal of Immunology
Volume180
Issue number1
StatePublished - Jan 1 2008
Externally publishedYes

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Calcineurin
T-Lymphocytes
Apoptosis
Thymocytes
TCF Transcription Factors
Interleukin-15
Interleukin-7
Calmodulin
Phosphoric Monoester Hydrolases
Interleukin-2
Protein Isoforms
Transcription Factors
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Manicassamy, S., Gupta, S., Huang, Z., Molkentin, J. D., Shang, W., & Sun, Z. (2008). Requirement of calcineurin Aβ for the survival of naive T cells. Journal of Immunology, 180(1), 106-112.

Requirement of calcineurin Aβ for the survival of naive T cells. / Manicassamy, Santhakumar; Gupta, Sonal; Huang, Zhaofeng; Molkentin, Jeffery D.; Shang, Weirong; Sun, Zuoming.

In: Journal of Immunology, Vol. 180, No. 1, 01.01.2008, p. 106-112.

Research output: Contribution to journalArticle

Manicassamy, S, Gupta, S, Huang, Z, Molkentin, JD, Shang, W & Sun, Z 2008, 'Requirement of calcineurin Aβ for the survival of naive T cells', Journal of Immunology, vol. 180, no. 1, pp. 106-112.
Manicassamy S, Gupta S, Huang Z, Molkentin JD, Shang W, Sun Z. Requirement of calcineurin Aβ for the survival of naive T cells. Journal of Immunology. 2008 Jan 1;180(1):106-112.
Manicassamy, Santhakumar ; Gupta, Sonal ; Huang, Zhaofeng ; Molkentin, Jeffery D. ; Shang, Weirong ; Sun, Zuoming. / Requirement of calcineurin Aβ for the survival of naive T cells. In: Journal of Immunology. 2008 ; Vol. 180, No. 1. pp. 106-112.
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