Held K, Bhonsle-Deeng L, Siewert K, Sato W, Beltrán E, Schmidt S, Rühl G, Ng JK, Engerer P, Moser M, Klinkert WE, Babbe H, Misgeld T, Wekerle H, Laplaud DA, Hohlfeld R, Dornmair K.
αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell-related features.Neurol Neuroimmunol Neuroinflamm. 2015 May 7;2(4):e107
OBJECTIVES:To characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8(+) T cells from an index patient who we followed for 18 years.
METHODS:We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed.
RESULTS:We found that a TCR Vβ1(+) T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2(+) α chains, including a Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the Vα7.2(+) MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years.
CONCLUSIONS:Our observation that a massively expanded TCR Vβ1 chain paired with distinct yet closely related MAIT cell-related α chains strongly points to an antigen-driven process in early active MS brain lesions.
The T cell receptor is made up of an alpha and beta chain and there are a number of genetic variants. In ancient immunological history there was a story that there a restricted T cell V beta usage of T cells in MS. This was supported that many disease causing cells in PL mice and Lewis rats were Variable beta (Vb) eight expressing. This did not pan out when other studies looked at diferent mice and rat CD4 responses. In this study they find alot of Vb1 expressing T CD8 positive T cells and suggests that they are expanded in the brain and were found in the blood. Many cells also expressed a V alpha 7 variant but there was a common found in mucosal associated invariant T cells, which correlate with the numbers of NKT and NK cells. Their presence decreased with time. Is this evidence that they are pathogenic and it this immunity burns out with time. In other studies these MAIT cells showed a suppressive activity against IFN-γ production by T cells in vitro. This suppression required cell contact but was independent of IL-10, inducible co-stimulator or the presence ,of B cells. So are they present and as they disappear does progression set in. More studies to find out
Labels: CD8 T cells