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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3622

Title: Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements
Authors: STINISSEN, Piet
VANDEVYVER, Caroline
MEDAER, Rob
VANDEGAER, L
NIES, J
TUYLS, L
HAFLER, DA
RAUS, Jef
Zhang, JK
Issue Date: 1995
Publisher: AMER ASSOC IMMUNOLOGISTS
Citation: JOURNAL OF IMMUNOLOGY, 154(9). p. 4883-4894
Abstract: Infiltrating gamma delta T cells are potentially involved in the central nervous system demyelination in multiple sclerosis (MS). To further study this hypothesis, we analyzed the frequency and functional properties of gamma delta T cells in peripheral blood (PB) and paired cerebrospinal fluid (CSF) of patients with MS and control subjects, including patients with other neurologic diseases (OND) and healthy individuals. The frequency analysis was performed under limiting dilution condition using rIL-2 and PHA. After PHA stimulation, a significantly increased frequency of gamma delta T cells was observed in PB (14.7 X 10(-4)) and in CSF (15.8 x 10(-4)) of MS patients as compared with 4.3 x 10(-4) in PB and 3.9 X 10(-4) detected in CSF of patients with OND. The frequency was represented equally in ND patients and normal individuals. Similarly, the IL-2-responsive gamma delta T cells occurred at a higher frequency in PB of MS (6.2 x 10(-4)) than in PB of control subjects (1.1 x 10(-4) in OND patients and 1.5 x 10(-4) in normal individuals). Forty-three percent (13 of 30) of the gamma delta T cell clones isolated from PB and CSF of MS patients responded to heat shock protein (HSP70) but not HSP65, whereas only 2 of 30 control gamma delta T cell clones reacted to the HSP. The majority of the gamma delta T cell clones were able to induce non-MHC-restricted cytolysis of Daudi cells. All clones displayed a substantial reactivity to bacterial superantigens staphylococcal enterotoxin B and toxic shock syndrome toxin-1, irrespective of their gamma delta V gene usage. Furthermore, the gamma delta T cell clones expressed predominantly TCRDV2 and CV2 genes (26 of 35 clones), whereas the clones derived from CSF of MS patients expressed either DV1 or DV2 genes. The obtained gamma delta clones, in general, represented rather heterogeneous clonal origins, even though a predominant clonal origin was found in a set of 10 gamma delta clones derived from one patient with MS. The present study provides new evidence supporting a possible role of gamma delta T cells in the secondary inflammatory processes in MS.
Notes: DR L WILLEMS INST,BIOTECHNOL UNIT,B-3590 DIEPENBEEK,BELGIUM. MS CLIN & REHABIL CTR,B-3900 OVERPELT,BELGIUM. SALVATOR HOSP,DEPT NEUROL,B-3500 HASSELT,BELGIUM. BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,DEPT MED,DIV NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. LIMBURGS UNIV CENTRUM,B-3590 DIEPENBEEK,BELGIUM.STINISSEN, P, DR L WILLEMS INST,MULTIPLE SCLEROSIS RES & IMMUNOL UNIT,UNIV CAMPUS,B-3590 DIEPENBEEK,BELGIUM.
URI: http://hdl.handle.net/1942/3622
Link to publication: http://www.jimmunol.org/cgi/content/abstract/154/9/4883
ISI #: A1995QU82500072
ISSN: 0022-1767
Type: Journal Contribution
Appears in Collections: Research publications

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