Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Role of Interferon-Inducible Gene IFI202b in the Suppressive Capacity of CD8 Regulatory T Cells Induced in (NZB NZW) F1 (BWF1) Lupus Mice
Singh, Ram P., Dinesh, Ravi, Hahn, Bevra H.
The interferon-inducible Ifi 202 gene family has been implicated in the susceptibility of BWF1 mice to SLE, particularly as its increased expression may protect autoreactive B cells from apoptosis. CD8+ Tregs induced by a peptide tolerogen can suppress anti-DNA-producing B cells. We tested the potential role of Ifi202 in the suppressive capacity of CD8+T regulatory cells.
We compared 45,000 murine genes between peripheral white blood cells (WBC), CD4+T cells, and CD8+ T cells from pCons-tolerized vs. non-tolerized mice using Affymetrix Gene Chip array 430. 2.0. Validation of differentially expressed genes was performed by real-time PCR. Protein expression was determined by intracellular FACS staining and by Western blot analyses. Anti-DNA ab was measured by ELISA. Gene silencing studies were performed by incubation of CD8+T cells with the appropriate si RNA.
1- In CD8+T cells from BWF1 mice tolerized with pCons, the expression of interferon inducible gene IFI202b was increased more than two-fold beginning at one week following pCons administration and extending through four weeks after treatment, with a decrease at 6 weeks. 2-In vitro re-stimulation with pCons or polyclonal activation significantly increased IFI202b mRNA expression in tolerized CD8+T cells compared to cells from untolerized mice. 3- Silencing of IFI202b abrogated the suppressive capacity of tolerized CD8+T cells on syngeneic CD4+CD25- T cells and on anti-DNA production. Silencing did not affect the susceptibility of CD8+Treg to apoptosis. In contrast, the silencing of IFNar1 (also upregulated in expression) did not affect the ability of CD8+T cells to suppress autoantibody production. 4- Lastly, the silencing of IFI202b decreased mRNA and protein expression of TGFb - a major mediator of suppression by CD8+T regulatory T cells.
In conclusion, increased expression of IFI202b in induced CD8+Treg cells contributes to their suppressive capacity, probably by decreasing the expression of TGFb.
To cite this abstract, please use the following information:
Singh, Ram P., Dinesh, Ravi, Hahn, Bevra H.; Role of Interferon-Inducible Gene IFI202b in the Suppressive Capacity of CD8 Regulatory T Cells Induced in (NZB NZW) F1 (BWF1) Lupus Mice [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1028