TY  - JOUR
AU  - Zhan, YF
AU  - Funda, DP
AU  - Every, AL
AU  - Fundova, P
AU  - Purton, JF
AU  - Liddicoat, DR
AU  - Cole, TJ
AU  - Godfrey, DI
AU  - Brady, JL
AU  - Mannering, SI
AU  - Harrison, LC
AU  - Lew, AM
Y2  - 2014/05/21
Y1  - 2004/09/01
SN  - 0953-8178
UR  - http://hdl.handle.net/11343/26392
AB  - T lymphocytes (pivotal in many inflammatory pathologies) are targets for glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We delineated here the expression of a recently identified glucocorticoid-induced TNF receptor (GITR) induced by GC and by TCR-mediated T-cell activation in GC receptor (GR)-deficient mice (GR-/-). We also compared the action of GC on GITR+ and GITR- T cells by monitoring apoptosis, proliferation and cytokine production stimulated by anti-CD3 antibody. By using GR-/- mice, we observed that the development of GITR+ T cells (both in thymus and periphery) is not dependent upon GR signaling. This contradicts the implication of GITR's name reflecting GC induction. TCR-mediated T-cell activation induced GITR expression in both GR+/+ and GR-/- cells. Somewhat unexpectedly, there was very modest GITR upregulation on GR+/+ T cells by a range of GC doses (10(-8) to 10(-6) M). Constitutive expression of GITR by a subset of CD4+ cells did not significantly render them resistant to GC-induced cell death. However, TCR-induced GITR upregulation on GR+/+ T cells was correlated with resistance to GC-mediated apoptosis suggesting that GITR, in conjunction with other (as yet unidentified) TCR-induced factors, protects T cells from apoptosis. Thus, even though GC is a potent inducer of apoptosis of T cells, activated T cells are resistant to GC-mediated killing. Meanwhile, although GC suppressed anti-CD3-induced cytokine production, cell proliferation was unaffected by GC in GR+/+ mice. GR deficiency has no effect on anti-CD3-induced cytokine production and proliferation. Our findings also have implications for GC treatment in that it would be more difficult to abrogate an ongoing T-cell mediated inflammatory response than to prevent its induction.
N1  - application/pdf
LA  - English
PB  - OXFORD UNIV PRESS
KW  - Cellular Immunology; Immune System and Allergy
T1  - TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death
DO  - 10.1093/intimm/dxh134
IS  - INTERNATIONAL IMMUNOLOGY
VL  - 16
IS  - 9
SP  - 1315-1321
L1  - /bitstream/handle/11343/26392/116182_5232.pdf?sequence=1&isAllowed=n
ER  -