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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3612

Title: Increased frequency of interleukin 2-responsive t-cells specific for myelin basic-protein and proteolipid protein in peripheral-blood and cerebrospinal-fluid of patients with multiple-sclerosis
Authors: Zhang, J
Markovic-Plese, Silva
LACET, B
RAUS, Jef
WEINER, HL
HAFLER, DA
Issue Date: 1994
Publisher: ROCKEFELLER UNIV PRESS
Citation: JOURNAL OF EXPERIMENTAL MEDICINE, 179(3). p. 973-984
Abstract: Equal numbers of CD4(+) T cells recognizing myelin basic protein (MBP) and proteolipid protein (PLP) are found in the circulation of normal individuals and multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive T cells are critical for the pathogenesis of MS, they would exist in a different state of activation as compared with myelin-reactive T cells cloned from the blood of normal individuals. This was investigated in a total of 62 subjects with definitive MS. While there were no differences in the frequencies of MBP- and PLP-reactive T cells after primary antigen stimulation, the frequency of MBP or PLP but not tetanus toxoid-reactive T cells generated after primary recombinant interleukin (rIL-2) stimulation was significantly higher in MS patients as compared with control individuals. Primary rIL-2-stimulated MBP-reactive T cell lines were CD4(+) and recognized MBP epitopes 84-102 and 143-168 similar to MBP-reactive T cell lines generated with primary MBP stimulation. In the cerebrospinal fluid (CSF) of MS patients, MBP-reactive T cells generated with primary rIL-2 stimulation accounted for 7% of the IL-2-responsive cells, greater than 10-fold higher than paired blood samples, and these T cells also selectively recognized MBP peptides 84-102 and 143-168. In striking contrast, MBP-reactive T cells were not detected in CSF obtained from patients with other neurologic diseases. These results provide definitive in vitro evidence of an absolute difference in the activation state of myelin-reactive T cells in the central nervous system of patients with MS and provide evidence of a pathogenic role of autoreactive T cells in the disease.
Notes: BRIGHAM & WOMENS HOSP,DEPT MED,DIV NEUROL,CTR NEUROL DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. DR L WILLEMS INST,MULTIPLE SCLEROSIS RES LAB,B-3590 DIEPENBEEK,BELGIUM.
URI: http://hdl.handle.net/1942/3612
Link to publication: http://www.jem.org/cgi/content/abstract/179/3/973
ISI #: A1994MY48400021
ISSN: 0022-1007
Type: Journal Contribution
Appears in Collections: Research publications

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