Inhibition of collagen-induced arthritis by DNA vaccines encoding TCR Vbeta5.2 and TCR Vbeta8.2 / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 1039-1048, 2009.
Article
in English
| WPRIM
| ID: wpr-279786
ABSTRACT
<p><b>BACKGROUND</b>Arthritogenic T lymphocytes with common T cell receptor (TCR) Vbeta clonotypes, infiltrating in the articulars of rheumatoid arthritis (RA) patients, play a central role in the pathogenesis of RA. TCR Vbeta5.2 and TCR Vbeta8.2 are the main pathogenic T cell clonotypes in the course of collagen-induced arthritis (CIA) progression in Lewis rats. To investigate a TCR-based immunotherapy for RA, we constructed recombinant DNA vaccines encoding TCR Vbeta5.2 and TCR Vbeta8.2, and evaluated the inhibitive effects of the two vaccines on CIA rats.</p><p><b>METHODS</b>Genes encoding TCR Vbeta5.2 and TCR Vbeta8.2 were amplified by RT-PCR from spleen lymphocytes of Lewis rats and cloned into the eukaryotic expression vector pTargeT. The expression of vaccines was confirmed by RT-PCR and immunohistochemistry. The inhibitive effects of the vaccines on articulars of CIA rats were assessed with arthritis index evaluation and histology. Interferon gamma (IFN-gamma) and interleukin (IL)-4 production by spleen lymphocytes were tested with enzyme-linked immunospot assay (ELISPOT) technique, the changes in peripheral CD4(+) and CD8(+) lymphocyte populations were tested by flow cytometry, and the level of anti-CII antibody in serum was assayed by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Recombinant DNA vaccines pTargeT-TCR Vbeta5.2 and pTargeT-pTCR Vbeta8.2 were successfully constructed. Both vaccines inhibited CIA, which alleviated the arthritis index score (P < 0.05), decreased the level of IFN-gamma (P < 0.05), and reduced the ratio of CD4(+)/CD8(+) lymphocytes (P < 0.05) and the anti-CII antibody in serum (P < 0.05). In addition, the histological change in DNA-vaccinated rats was less serious than CIA rats. Compared to pTCR Vbeta 8.2 and pTCR Vbeta 5.2 groups, the group that was injected with a combination of the two vaccines showed stronger inhibitive effects on CIA than either individual vaccine.</p><p><b>CONCLUSION</b>The recombinant plasmids pTargeT-TCR Vbeta5.2 and pTargeT-TCR Vbeta8.2 have obvious inhibatory effects on CIA rats and better effects could be achieved when the vaccines were used in combination.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Peptide Fragments
/
Pharmacology
/
Arthritis, Experimental
/
Rats, Inbred Lew
/
Enzyme-Linked Immunosorbent Assay
/
Immunohistochemistry
/
CD4-Positive T-Lymphocytes
/
Interleukin-4
/
Interferon-gamma
/
Receptors, Antigen, T-Cell, alpha-beta
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2009
Type:
Article
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