Background 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).
Objectives 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
Methods CD8+ T cell inhibition assay. 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).
CD8 cell booster. 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.
Results We compared 3 Sjogren's 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
Conclusions 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
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
Disclosure of Interest None declared