TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes

Ramireddy Bommireddy, Vijay Saxena, Ilona Ormsby, Moying Yin, Gregory P. Boivin, George F. Babcock, Ram R. Singh, Thomas C Doetschman

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

TGF-β1 plays an important role in the maintenance of immune homeostasis and self-tolerance. To determine the mechanism by which TGF-β1 prevents autoimmunity we have analyzed T cell activation in splenic lymphocytes from TGF-β1 -deficient mice. Here we demonstrate that unlike wild-type splenic lymphocytes, those from Tgfb1-/- mice are hyporesponsive to receptor-mediated mitogenic stimulation, as evidenced by diminished proliferation and reduced IL-2 production. However, they have elevated levels of IFN-γ and eventually undergo apoptosis. Receptor-independent stimulation of Tgfb1-/- T cells by PMA plus ionomycin induces IL-2 production and mitogenic response, and it rescues them from anergy. Tgfb1-/- T cells display decreased CD3 expression; increased expression of the activation markers LFA-1, CD69, and CD122; and increased cell size, all of which indicate prior activation. Consistently, mutant CD4+ T cells have elevated intracellular Ca2+ levels. However, upon subsequent stimulation in vitro, increases in Ca2+ levels are less than those in wild-type cells. This is also consistent with the anergic phenotype. Together, these results demonstrate that the ex vivo proliferative hyporesponsiveness of Tgfb1-/- splenic lymphocytes is due to prior in vivo activation of T cells resulting from deregulated intracellular Ca2+ levels.

Original languageEnglish (US)
Pages (from-to)4612-4622
Number of pages11
JournalJournal of Immunology
Volume170
Issue number9
StatePublished - May 1 2003
Externally publishedYes

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Homeostasis
Lymphocytes
Apoptosis
T-Lymphocytes
Interleukin-2
Self Tolerance
Lymphocyte Function-Associated Antigen-1
Ionomycin
Autoimmunity
Cell Size
Maintenance
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Bommireddy, R., Saxena, V., Ormsby, I., Yin, M., Boivin, G. P., Babcock, G. F., ... Doetschman, T. C. (2003). TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. Journal of Immunology, 170(9), 4612-4622.

TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. / Bommireddy, Ramireddy; Saxena, Vijay; Ormsby, Ilona; Yin, Moying; Boivin, Gregory P.; Babcock, George F.; Singh, Ram R.; Doetschman, Thomas C.

In: Journal of Immunology, Vol. 170, No. 9, 01.05.2003, p. 4612-4622.

Research output: Contribution to journalArticle

Bommireddy, R, Saxena, V, Ormsby, I, Yin, M, Boivin, GP, Babcock, GF, Singh, RR & Doetschman, TC 2003, 'TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes', Journal of Immunology, vol. 170, no. 9, pp. 4612-4622.
Bommireddy R, Saxena V, Ormsby I, Yin M, Boivin GP, Babcock GF et al. TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. Journal of Immunology. 2003 May 1;170(9):4612-4622.
Bommireddy, Ramireddy ; Saxena, Vijay ; Ormsby, Ilona ; Yin, Moying ; Boivin, Gregory P. ; Babcock, George F. ; Singh, Ram R. ; Doetschman, Thomas C. / TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. In: Journal of Immunology. 2003 ; Vol. 170, No. 9. pp. 4612-4622.
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