[Effect of dendritic cells pulsed with Talpha146-162 on autoimmune myasthenia graves and the role of B cells activation]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;40(5):793-7.
[Article in Chinese]

Abstract

Objective: To explore the therapeutic effect of Talpha146-162-iMDCs on C57BL/6 mice with EAMG and the role of changes in B cell activation regulated by Cbl.

Methods: Thirty four adult male C57BL/6 mice were randomly divided into EAMG group (A group), EAMG group with interventions (B group) and control group (C group). T-AChR antigens were injected to the mice in A and B groups to induce EAMG. Meanwhile, dendritic cells from immature bone marrows were cultured and pulsed with Talpha146-162, and injected to the mice in the intervention group. The mRNA expression of Cbl was detected by RT-PCR 90 days after the termination of experiment. The expression and phosphorylation of Syk and Lyn proteins were measured by Western blot.

Results: More mice (9/12, 75%) in A group developed EAMG than in B group (3/12, 25%, P<0.05). Mice in A group also suffered more serious illness in terms of clinical scores than mice in B group (1.69+/-1.12 vs 0.35+/-0.67, P<0.01). No EAMG occurred in mice in C group. Mice in B group had lower mRNA expressions of Cbl in the spleens and lymphonodes than mice in A groups, but both had higher expressions than mice in C group (P<0.05). Mice in B group had higher mRNA expression of Cbl than mice in A group (P<0.05).

Conclusion: Talpha146-162-iMDCs prevent EAMG, possibly through negative regulation of Cbl on BCR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-cbl / genetics
  • Proto-Oncogene Proteins c-cbl / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Random Allocation
  • Receptors, Cholinergic / immunology*
  • Syk Kinase
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, Cholinergic
  • Proto-Oncogene Proteins c-cbl
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Cbl protein, mouse