Intracellular Ca2+ Elevation and Cyclosporin A Synergistically Induce TGF-β1-Mediated Apoptosis in Lymphocytes Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Calcium
  • Cyclosporine
  • Lymphocyte Subsets
  • Transforming Growth Factor beta

abstract

  • Apoptosis plays an essential role in the development and homeostasis of the immune system. During lymphocyte development, potentially autoreactive cells are eliminated via the activation of a tightly regulated cell death program(s). Similar processes operate in mature lymphocytes, to control the magnitude of the normal immune response by eliminating activated lymphocytes. However, differences in susceptibility to signal-induced apoptosis between immature and mature lymphocytes are numerous. One well-characterized example occurs in response to Ca2+ elevation: peripheral T lymphocytes are resistant, while immature thymocytes are highly susceptible, to Ca2+-mediated cell death (CMCD). In this study, we show that the immunosuppressant cyclosporin A (CsA) primes splenic lymphocytes to undergo CMCD upon ionomycin stimulation. This CsA-induced CMCD affected both T and B lymphocytes. CsA-plug Ca2+-mediated apoptosis was dissected into a two-step process: first, CsA and Ca2+ synergized to induce TGF-beta 1 secretion by B cells; and then TGF-beta 1 and Ca2+ synergistically triggered T and B lymphocyte apoptosis. Together, our results suggest that lymphocyte apoptosis may play a role in CsA-induced immunosuppression via a TGF-beta-dependent mechanism.

publication date

  • March 15, 1997

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 9058783

Additional Document Info

start page

  • 2527

end page

  • 34

volume

  • 158

number

  • 6