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CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis.
- Source :
-
Arthritis and rheumatism [Arthritis Rheum] 2003 May; Vol. 48 (5), pp. 1452-60. - Publication Year :
- 2003
-
Abstract
- Objective: CD4+,CD25+ T regulatory cells may offer opportunities to intervene in the course of autoimmune disease. We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen-induced arthritis (CIA).<br />Methods: We depleted DBA/1 mice of CD25+ regulatory cells by injection of a depleting monoclonal antibody specific for CD25 14 days before a single immunization with type II collagen (CII) in Freund's complete adjuvant. CD4+,CD25+ T cells were adoptively transferred to some groups of mice during immunization. Mice were then scored for signs of arthritis, and blood was taken periodically to measure the amounts of CII-specific antibodies. Splenocytes of treated mice were examined in vitro to determine the effects of depletion on proliferation to CII and control antigens.<br />Results: CD25+ cell-depleted DBA/1 mice had significantly more severe disease than control mice following collagen immunization. The magnified severity was also accompanied by higher antibody titers against collagen, and in vitro tests showed increased proliferation of collagen-specific T cells. Adoptively transferring CD4+,CD25+ T cells into depleted mice was shown to reverse the heightened severity. Control mice, which were depleted and immunized with the neoantigen keyhole limpet hemocyanin (KLH), had neither an increased antibody response toward KLH nor an augmented proliferative response, indicating that CD25+ cell depletion preferentially affects immunity against self antigen.<br />Conclusion: These results establish a link between CD4+,CD25+ regulatory cells and CIA and provide a rationale for investigating CD4+,CD25+ T regulatory cells in the treatment and prevention of arthritis.
- Subjects :
- Adoptive Transfer
Animals
Antibodies, Monoclonal pharmacology
Arthritis, Experimental metabolism
Arthritis, Experimental physiopathology
CD4 Antigens biosynthesis
CD4 Antigens immunology
Cell Division
Collagen Type II immunology
Collagen Type II pharmacology
Edema chemically induced
Edema pathology
Edema physiopathology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Forelimb pathology
Freund's Adjuvant immunology
Freund's Adjuvant pharmacology
Hemocyanins immunology
Hemocyanins pharmacology
Hindlimb pathology
Immunization
Male
Mice
Mice, Inbred DBA
Rats
Receptors, Interleukin-2 biosynthesis
Spleen cytology
Spleen drug effects
Spleen immunology
T-Lymphocytes metabolism
T-Lymphocytes transplantation
Antibodies, Monoclonal immunology
Arthritis, Experimental immunology
Lymphocyte Depletion
Receptors, Interleukin-2 immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0004-3591
- Volume :
- 48
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 12746920
- Full Text :
- https://doi.org/10.1002/art.11063