Clonal Expansions of Cd8+ T Cells Dominate the T Cell Infiltrate in Active Multiple Sclerosis Lesions as Shown by Micromanipulation and Single Cell Polymerase Chain Reaction

By Holger Babbe, Axel Roers, A. Waisman, Hans Lassmann, N. Goebels, R. Hohlfeld, M. Friese, Roland Schröder, M. Deckert, S. Schmidt and 2 more. Journal of Experimental Medicine, 2000

1,005 citations recorded by the source corpus.

Clonal composition and T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level of single cells. Individual CD4+ or CD8+ T cells were isolated from frozen sections of lesional tissue by micromanipulation and subjected to single target amplification of TCR-β gene rearrangements. This strategy allows the assignment of a TCR variable region (V region) sequence to the particular T cell from which it was amplified. Sequence analysis revealed that in both cases investigated, the majority of CD8+ T cells belonged to few clones. One of these clones accounted for 35% of CD8+ T cells in case 1. V region sequence comparison revealed signs of selection for common peptide specificities for some of the CD8+ T cells in case 1. In both cases, the CD4+ T cell population was more heterogeneous. Most CD4+ and CD8+ clones were represented in perivascular infiltrates as well as among parenchymal T cells. In case 2, two of the CD8+ clones identified in brain tissue were also detected in peripheral blood. Investigation of the antigenic specificities of expanded clones may help to elucidate their functional properties.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/2321bad2d647d841893190ac50355544e9bac57b

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In Immunology

1. R. Ransohoff
2. Hans Lassmann
3. Roland Martin
4. Berislav Zlokovic
5. J. Buckner
6. C. Iadecola
7. J. Goverman

In Oncology

1. Hans Lassmann
2. P. Kivisäkk
3. G. Kidd
4. R. Ransohoff

Citations in the corpus

• Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. (2006, background): “This is particularly important, since CD8 + T cells are a major component of the inflammatory infiltrate in multiple sclerosis lesions (Babbe et al., 2000; Neumann et al., 2002).”
• The relation between inflammation and neurodegeneration in multiple sclerosis brains (2009, result): “Consistent with prior studies (Gay et al., 1997; Babbe et al., 2000), a sub-analysis of CD4 and CD8 positive T cells revealed that the majority of T-cell infiltration in multiple sclerosis lesions consisted of CD8 positive T cells (data not shown).”
• Three or more routes for leukocyte migration into the central nervous system (2003, result): “Recent results indicate that CD8 + T cells can mediate EAE and they are the main population that is clonally expanded in the brain of individuals with M”
• Immunology of multiple sclerosis. (2005, neutral): “The reduced number of peptideoccupied HLA class I molecules in MS patients (29), the CD8+ T cell infiltrations in the CSF and MS plaque tissue (30, 31), and the higher expression of HLA class I in the brain (32) suggest that the roles of HLA class I, CD8+ T cells, and NK cells merit further study.”
• Multiple Sclerosis Pathology. (2018, background): “2D) and, in some cases, immunoglobulin-containing plasma cells (Babbe et al. 2000; Frischer et al. 2009).”
• Multiple sclerosis: a complicated picture of autoimmunity (2007, background): “Also, examination of brain tissue from patients with multiple sclerosis has shown clonal expansion of CD8 + T cells in lesions based on T cell receptor analysi”
• New concepts in the immunopathogenesis of multiple sclerosis (2002, neutral): “By analysing single cells from lesions or CSF of patients with MS, two group”