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-β1 secretion by B cells; and then TGF-β1 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-β-dependent mechanism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2527-2534 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 158 |
| Issue number | 6 |
| State | Published - Mar 15 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Intracellular Ca2+ Elevation and Cyclosporin A Synergistically Induce TGF-β1-Mediated Apoptosis in Lymphocytes. / Andjelić, Sofija; Khanna, Ashwani; Suthanthiran, Manikkam; Nikolich-Zugich, Janko.
In: Journal of Immunology, Vol. 158, No. 6, 15.03.1997, p. 2527-2534.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intracellular Ca2+ Elevation and Cyclosporin A Synergistically Induce TGF-β1-Mediated Apoptosis in Lymphocytes
AU - Andjelić, Sofija
AU - Khanna, Ashwani
AU - Suthanthiran, Manikkam
AU - Nikolich-Zugich, Janko
PY - 1997/3/15
Y1 - 1997/3/15
N2 - 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-β1 secretion by B cells; and then TGF-β1 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-β-dependent mechanism.
AB - 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-β1 secretion by B cells; and then TGF-β1 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-β-dependent mechanism.
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M3 - Article
VL - 158
SP - 2527
EP - 2534
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -