Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration

Autor: Albert, L M, Austin, L M, Darnell, R B
Přispěvatelé: Laboratory of Molecular Neuro-oncology, Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York], Laboratory for Investigative Dermatology [New York], Rockefeller University [New York]
Jazyk: angličtina
Rok vydání: 2000
Předmět:
Zdroj: Annals of Neurology
Annals of Neurology, Wiley, 2000, pp.9-17. ⟨10.1002/1531-8249(200001)47:13.0.CO;2-I⟩
ISSN: 0364-5134
1531-8249
DOI: 10.1002/1531-8249(200001)47:13.0.CO;2-I⟩
Popis: International audience; Patients with paraneoplastic cerebellar degeneration (PCD) offer the opportunity to explore the mechanisms underlying tumor immunity and immune-mediated neuronal degeneration. Cytotoxic T lymphocytes (CTLs) specific for the PCD onconeural antigen cdr2 found in the blood of patients with PCD are likely to be effectors of PCD tumor immunity. Here, we suggest a role for CTLs in the autoimmune destruction of Purkinje neurons. More than 75% of the cells obtained from the cerebrospinal fluid (CSF) of PCD patients were CD3+ alphabeta T cells. In patients with active/progressive disease, 20% to 40% of CSF cells were activated T cells, and the CD4+ helper cells were Th1-type cells. Three PCD patients were given tacrolimus, a specific inhibitor of activated T cells, which markedly reduced these cells in the CSF. Tacrolimus also reduced the number of activated cdr2-specific CTLs in the peripheral blood, but did not lead to tumor recurrence. We suggest that activated cdr2-specific CTLs in the CSF contribute to Purkinje degeneration in PCD, and that tacrolimus therapy may benefit patients with paraneoplastic neurological disease and other T cell-mediated autoimmune neurological disorders.
Databáze: OpenAIRE
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