AB0186 The Role of the Avidity Model of T Cell Regulation in Sjogren's Syndrome
Authors: O. Petryna, L. Chess
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> A subset Qa-1/HLA-E-restricted CD8+ T cells (CD8(H)), which functions in mediating self-nonself discrimination was found to serve a crucial immunoregulatory function in man. Its target was identified in humans as the heat shock protein leader sequence peptide Hsp60sp bound to HLA –E, expressed on effector CD4+ T cells (3-5). <h3>Objectives</h3> Compared with normal healthy individuals, data from 10 T1D patients showed that in the majority of the T1D patients tested, there is a defect in HLA-E-restricted CD8+ T cell regulatory (1-3). Here we provide evidence that patients with Sjogrens syndrome also display a defect in HLA-E restricted regulatory cells <h3>Methods</h3> <i>CD8+ T cell inhibition assay.</i> Target HLA-E–transfected cells (B721/E) were loaded with Hsp60sp and B7sp. CD8 (H) were added. We studied the CD8(H) inhibition of target B721/E cells loaded with Hsp60sp. We tested the effect of the CD8(H) lines on the avidity of immune responses to self-antigen myelin basic protein (MBP) versus those to foreign antigen tetanus toxoid (TT). <i>CD8 cell booster.</i> DCs were loaded with either Hsp60sp and planted into CD8+ T cells cultures from the test group. Hsp60sp-boosted CD8(H) cells were studied in assays as above. <h3>Results</h3> We compared 3 Sjogren9s patients (SjS) to 4 healthy controls. The CD8(H) lines of healthy controls consistently suppressed B721/E cells loaded with Hsp60sp but, while CD8(H) cells form SjS lacked the ability to suppress same target (Table 1). CD8(H) cells of the control inhibited immune response to MBP self-antigen. Such regulatory function was impaired in tested SjS. DC cell booster restored the ability of CD8(H)T cells of the test group to regulate activated CD4 cells <h3>Conclusions</h3> Here we provide evidence that patients with Sjogrens syndrome display a defect in HLA-E restricted regulatory cells, reflected as a functional abnormality in the specific recognition of HLE bound Hsp60sp by the HLA-E restricted CD8+ T cells. This mechanism may be critical in the control of distinct autoimmune diseases and may serve as a potential therapeutic target <h3>References</h3> Jiang H, Wu Y, Liang B, Zheng Z, Tang G, Kanellopoulos J, et al. An affinity/avidity model of peripheral T cell regulation. J Clin Invest. 2005 Feb;115(2):302-12. PubMed PMID: 15668735. Pubmed Central PMCID: 544609. Epub 2005/01/26. eng. Jiang H, Chess L. How the immune system achieves self-nonself discrimination during adaptive immunity. Adv Immunol. 2009;102:95-133. PubMed PMID: 19477320. Epub 2009/05/30. eng. Eardley DD, Hugenberger J, McVay-Boudreau L, Shen FW, Gershon RK, Cantor H. Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med. 1978 Apr 1;147(4):1106-15. PubMed PMID: 306405. Pubmed Central PMCID: 2184236. Epub 1978/04/01. eng. Cantor H, Hugenberger J, McVay-Boudreau L, Eardley DD, Kemp J, Shen FW, et al. Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. J Exp Med. 1978 Oct 1;148(4):871-7. PubMed PMID: 308990. Pubmed Central PMCID: 2185021. Epub 1978/10/01. eng. Jiang H, Chess L. An integrated model of immunoregulation mediated by regulatory T cell subsets. Adv Immunol. 2004;83:253-88. PubMed PMID: 15135634. Epub 2004/05/12. eng <h3>Disclosure of Interest</h3> None declared