Japanese Journal of Rheumatology

, Volume 7, Issue 1, pp 35–45 | Cite as

Methyl-vitamin B12 blocks the CD28 co-stimulatory pathway in human T cells and its possible therapeutic application for T cell-mediated diseases, including rheumatoid arthritis

  • Hiroko Nagafuchi
  • Noboru Suzuki
  • Mitsuhiro Takeno
  • Tsuyoshi Sakane
Original Article


The effects of metyl-vitamin B12 have been examined on human T cell activation induced by stimulation of T cell receptor (TCR)-CD3 and an accessory molecule, CD28. When T cells in the presence of 10% mitomycin-treated non-T cells were stimulated with anti-CD3 mAb at the optimal concentration, methyl-B12 did not inhibit T cell proliferation. However, when T cells were stimulated with the suboptimal concentration of anti-CD3 and anti-CD28 mAbs, methyl-B12 exhibited potent inhibition of T cell proliferation. Methyl-B12 did not affect cell surface expression of the CD3 and CD28 molecules of T cells. Methyl-B12 inhibited a 29 kDa protein tyrosine phosphorylation that was specifically induced by anti-CD3 and anti-CD28 mAbs. Similarly, T cell proliferation of patients with rheumatoid arthritis (RA), which is representative of T cell-mediated disease was inhibited by methyl-B12, when T cells were stimulated by anti-CD3 and anti-CD28 mAbs. These results suggest that methyl-B12 modulates lymphocyte function through blockade of the CD28 signaling pathway and that methyl-B12 may have T cell inhibitory activity that is applicable for treating patients with RA.

Key words

methyl-B12 CD28 T lymphocytes humans rheumatoid arthritis 


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Copyright information

© VSP and Japanese Rheumatism Association 1997

Authors and Affiliations

  • Hiroko Nagafuchi
    • 1
  • Noboru Suzuki
    • 1
  • Mitsuhiro Takeno
    • 2
  • Tsuyoshi Sakane
    • 2
  1. 1.Division of Allergy and Rheumatic Diseases, Institute of Medical ScienceSt. Marianna University School of MedicineKawasaki, KanagawaJapan
  2. 2.Department of Immunology and Medical ZoologySt. Marianna University School of MedicineKawasaki, KanagawaJapan

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