Correspondence

Mast Cells and the Mediation of T-Cell Recruitment in Arthritis

N Engl J Med 2003; 349:1294September 25, 2003

Article

To the Editor:

The article by Woolley (April 24 issue)1 is timely but incomplete. Not mentioned are findings about the role of mast cells in the local recruitment of effector T cells in arthritis. Studies of T-cell–mediated contact and delayed-type hypersensitivity in mice have shown that antibodies have a crucial initiating role through the activation of mast cells by complement C5a. Mast cells release vasoactive mediators, such as tumor necrosis factor α, which stimulate the local endothelium to optimize the local recruitment of T cells.2-4 Thus, soon after immunization, B-1 B cells produce antigen-specific IgM antibodies, and later, B-2 cells produce IgG antibodies and later still, IgE antibodies that initiate the recruitment of T cells into the tissues.4 Recent findings in experimental arthritis are probably related to this process, since roles for B cells,5 antibodies, complement,6 and mast cells have been described.

If this pathway for the recruitment of effector T cells by mast cells proves to be relevant to human arthritis, then the new focus on mast-cell–related treatments highlighted by Woolley has much broader implications. In addition, greater attention should be paid to antibody and complement, as well as to the development of mast-cell–directed therapies.

Philip W. Askenase, M.D.
Yale University School of Medicine, New Haven, CT 06520-8013
philip.askenase@yale.edu

6 References

1. 1

   Woolley DE. The mast cell in inflammatory arthritis. N Engl J Med 2003;348:1709-1711
   Full Text | Web of Science | Medline

2. 2

   Askenase PW, Bursztajn S, Gershon MD, Gershon RK. T cell-dependent mast cell degranulation and release of serotonin in murine delayed-type hypersensitivity. J Exp Med 1980;152:1358-1374
   CrossRef | Web of Science | Medline

3. 3

   Tsuji RF, Kawikova I, Ramabhadran R, et al. Early local generation of C5a initiates the elicitation of contact sensitivity by leading to early T cell recruitment. J Immunol 2000;165:1588-1598
   Web of Science | Medline

4. 4

   Tsuji RF, Szczepanik M, Kawikova I, et al. B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity. J Exp Med 2002;196:1277-1290
   CrossRef | Web of Science | Medline

5. 5

   Svensson L, Jirholt J, Holmdahl R, Jansson L. B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol 1998;111:521-526
   CrossRef | Web of Science | Medline

6. 6

   Wang Y, Kristan J, Hao L, Lenkoski CS, Shen Y, Matis LA. A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resistant to collagen-induced arthritis. J Immunol 2000;164:4340-4347
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Taxiarchis Kourelis, Duraisamy Kempuraj, Akrivi Manola, Theoharis C. Theoharides. 2010. Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases. , 103-145.
   CrossRef

2. 2

   Mai Zhang, Robin L. Thurmond, Paul J. Dunford. (2007) The histamine H4 receptor: A novel modulator of inflammatory and immune disorders. Pharmacology & Therapeutics 113:3, 594-606
   CrossRef

3. 3

   Theoharis C. Theoharides. 2006. Synovial Mast Cells in Inflammatory Arthritis. .
   CrossRef