Cellular environments and apoptosis: tissue microenvironments control activated T-cell death

doi:10.1016/S0167-5699(97)01003-7

Immunology Today

Volume 18, Issue 2, February 1997, Pages 72-76

Immunology Today

https://doi.org/10.1016/S0167-5699(97)01003-7 Get rights and content

Abstract

Activated T cells must he removed by apoptosis at the end of an immune response in order to maintain cellular homeostasis. Although recent attention has focused on the rule of CD95 (Fas/APO-1) in the elimination of activated T cells, apoptosis can also be induced by cytokine deprivation. Here, Arne Akbar and Mike Salmon describe how both death pathways interact in activated T cells and are profoundly influenced by different tissue microenvironments.

References (43)

P.M. Krammer et al.
Curr. Opin. Immunol.
(1994)
D.H. Lynch et al.
Immunol. Today
(1995)
A.K. Abbas
Cell
(1996)
A.N. Akbar et al.
Immunol. Today
(1993)
J.J. Cohen
Immunol. Today
(1993)
A. Strasser et al.
Cell
(1991)
L. van Parijs et al.
Immunity
(1996)
Y. Tamaru et al.
Blood
(1993)
T. Taniguchi et al.
Cell
(1993)
L.H. Boise et al.
Immunity
(1995)

E. Ayroldi et al.

Blood

(1995)

A. Cayota et al.

Blood

(1996)

A. Strasser

Curr. Opin. Immunol.

(1995)

J. Massague et al.

Curr. Opin. Genet. Dev.

(1995)

J. Wuarin et al.

Cell

(1996)

D.L. Vaux et al.

E.S. Razvi et al.

J. Virol.

(1993)

R. Ahmed et al.

Science

(1996)

A.N. Akbar et al.

J. Exp. Med.

(1993)

A.N. Akbar et al.

Eur. J. Immunol.

(1996)

H.E. Broome et al.

Immunology

(1995)

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ViewpointCellular environments and apoptosis: tissue microenvironments control activated T-cell death

Abstract

Curr. Opin. Immunol.

Immunol. Today

Cell

Immunol. Today

Immunol. Today

Cell

Immunity

Blood

Cell

Immunity

Blood

Blood

Curr. Opin. Immunol.

Curr. Opin. Genet. Dev.

Cell

J. Virol.

Science

J. Exp. Med.

Eur. J. Immunol.

Immunology

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Cellular environments and apoptosis: tissue microenvironments control activated T-cell death