Increased caspase-3 expression and activity contribute to reduced CD3zeta expression in systemic lupus erythematosus T cells.
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| Abstract |
T cells isolated from patients with systemic lupus erythematosus (SLE) express low levels of CD3zeta-chain, a critical molecule involved in TCR-mediated signaling, but the involved mechanisms are not fully understood. In this study we examined caspase-3 as a candidate for cleaving CD3zeta in SLE T cells. We demonstrate that SLE T cells display increased expression and activity of caspase-3. Treatment of SLE T cells with the caspase-3 inhibitor Z-Asp-Glu-Val-Asp-FMK reduced proteolysis of CD3zeta and enhanced its expression. In addition, Z-Asp-Glu-Val-Asp-FMK treatment increased the association of CD3zeta with lipid rafts and simultaneously reversed the abnormal lipid raft preclustering, heightened TCR-induced calcium responses, and reduced the expression of FcRgamma-chain exclusively in SLE T cells. We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3zeta-chain and suggest that such molecules can be considered in the treatment of this disease.
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| Authors | Sandeep Krishnan, Juliann G Kiang, Carolyn U Fisher, Madhusoodana P Nambiar, Hang T Nguyen, Vasileios C Kyttaris, Bhabadeb Chowdhury, Violeta Rus, George C Tsokos |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 5 Pg. 3417-23 (Sep 01 2005) ISSN: 0022-1767 [Print] United States |
| PMID | 16116236 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.) |
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