Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions.

Abstract

ABSTRACTyS T cells are a distinct lymphocyte population that can exhibit reactivity with heat shock proteins over- RESULTSAccumulation of y6T Cells in Acute MS Plques. a4and y8 T-cell populations were examined in frozen tissue specimens from five postmortem cases with MS, one case with subacute sclerosing panencephalitis (SSPE), and five cases without neurological disease. Frozen sections were stained with hematoxylin/eosin, oil red-O (ORO), and mAbs specific for CD2 and the interleukin 2 receptor. Both the clinical data and a detailed immunohistological analysis of these cases are published in another article with the same designations for CNS samples as in this report (10). Plaques with perivenular inflammation (Fig. 1), hypercellularity, and foamy macrophages containing ORO-positive degenerating myelin throughout the lesion were considered to be actively demyelinating (cases 285 and 194), while hypocellular ORO-and galactocerebroside-negative demyelinated plaques were classified as chronic lesions. Subacute plaques had ORO-positive cells only in the borders of demyelinated lesions (

Transendothelial Migratory Pathways of Vδ1+TCRγδ+ and Vδ2+TCRγδ+ T Lymphocytes from Healthy Donors and Multiple Sclerosis Patients: Involvement of Phosphatidylinositol 3 Kinase and Calcium Calmodulin-Dependent Kinase II

“…Thus, the two subsets use different adhesion molecules and signaling pathways to transmigrate, suggesting that resident and circulating ␥␦ T lymphocytes are equipped with distinct biochemical and molecular mechanisms to regulate their selective tissue localization. This might also account for the finding that in relapsing-remitting MS, ␥␦ T cells found in the lesions differ from those in CSF (5,6,12,31), supporting the hypothesis that the two ␥␦ T cell subsets play distinct roles in the pathogenesis of the disease.…”

“…Several cell types and soluble mediators contribute to the onset and progression of demyelinization, including T lymphocytes (2-4); in particular, some previous reports point to an active role played by the ␥␦ T cell subset in the pathogenesis of MS (5)(6)(7).…”

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

“…The description of such repeated sequences in the PBL of healthy donors is unprecedented since only a few V81-J81 sequences have been published to date (28)(29)(30)(31). Two studies showed an unrestricted repertoire in PBL from patients and normal controls, but predominant sequences in acute multiple sclerosis (29) and leprosy lesions (28), respectively, suggesting in situ selection of particular VIS1 + cells by so far undefined antigens. One further study demonstrated a restricted V/~I repertoire in the peripheral blood of certain patients with rheumatoid arthritis but not in four healthy controls (30).…”

“…In the present work, we have shown that V81-J81junctions, while displaying the extensive alterations of germline sequences that are characteristic of post fetal stages (14), are not randomly represented among PBL V/$1 + cells in a large fraction of healthy donors. The description of such repeated sequences in the PBL of healthy donors is unprecedented since only a few V81-J81 sequences have been published to date (28)(29)(30)(31). Two studies showed an unrestricted repertoire in PBL from patients and normal controls, but predominant sequences in acute multiple sclerosis (29) and leprosy lesions (28), respectively, suggesting in situ selection of particular VIS1 + cells by so far undefined antigens.…”

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

“…wide range of physiological functions, they may also be involved in autoimmunity (5)(6)(7). A striking example of a putatively autoimmune human ␥␦-TCR 2 was described in 1991 (8).…”