Abstract |
SLE and mixed connective tissue disease ( MCTD) are characterized by the presence of high titers of autoantibodies against uridine-rich RNA-small nuclear ribonucleoprotein ( snRNP) Ag. Because the presence of such snRNP-reactive autoantibodies has recently been shown to be associated with polymorphisms of HLA, this study was undertaken to determine whether snRNP-reactive T cells could be identified and characterized from patients. PBMC were stimulated with affinity-purified snRNP Ag and cloned by limiting dilution in the presence of rIL-2 and rIL-4, snRNP-reactive human T cell clones were generated from three patients and two healthy blood donors who possessed disease-associated HLA genotypes. The cell surface phenotype of clones determined by flow cytometry was CD3+, CD4+, CD45RO+, TCR V alpha beta+. TCR V beta analysis, performed using V beta-specific primers and polymerase chain reaction, revealed that the T cell lines generated were clonal; a limited number of TCR V beta genes were expressed among the clones tested. All clones tested by mAb blocking of Ag-induced proliferation were restricted by HLA-DR. Several T cell clones were identified that were specific for B'/B or D polypeptides. These results demonstrate that snRNP-reactive T cells can be isolated from SLE and MCTD patients in vitro, and that Ag-driven expansion of such T cells could play a role in the immunopathogenesis of these diseases in vivo.
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Authors | R W Hoffman, Y Takeda, G C Sharp, D R Lee, D L Hill, H Kaneoka, C W Caldwell |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 151
Issue 11
Pg. 6460-9
(Dec 01 1993)
ISSN: 0022-1767 [Print] United States |
PMID | 8245479
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- HLA-DR Antigens
- Receptors, Antigen, T-Cell, alpha-beta
- Ribonucleoproteins, Small Nuclear
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Topics |
- Adult
- Amino Acid Sequence
- Antibodies, Monoclonal
(immunology)
- Antigen-Presenting Cells
(physiology)
- Base Sequence
- Cell Line
- Clone Cells
- Female
- HLA-DR Antigens
(physiology)
- Humans
- Lupus Erythematosus, Systemic
(immunology)
- Lymphocyte Activation
- Male
- Middle Aged
- Mixed Connective Tissue Disease
(immunology)
- Molecular Sequence Data
- Receptors, Antigen, T-Cell, alpha-beta
(analysis)
- Ribonucleoproteins, Small Nuclear
(immunology)
- T-Lymphocytes
(immunology)
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