B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo

Michele M. Kosiewicz, Anasuya Krishnan, Mark T. Worthington, James A. Matriano, William G. Ross

Research output: Contribution to journalArticle

Abstract

Inducing apoptosis of activated lymphocytes via Fas ligand (FasL, CD95) may be a useful strategy for the treatment of autoimmune diseases mediated by pathogenic T cells. We propose that B cells may be ideal tools for effective delivery of a FasL-mediated apoptotic signal to pathogenic T cells for a variety of reasons, including their unique ability to efficiently take up and present antigen to T cells that share the same specificity. Here, we demonstrate that B cell clones engineered to express CD95 can effectively suppress a systemic primed antigen-specific T cell response in vivo. Intravenous injection of antigen-pulsed FasL-expressing B cells eliminated antigen-specific (TCR transgenic) T cells from the draining lymph nodes within 12-60 h, and suppressed a delayed-type hypersensitivity response in an antigen-specific manner. These results indicate that B cells can be engineered to express FasL, and used to impair T cell function in vivo, suggesting that FasL-expressing B cells may be an effective tool for the treatment of established T cell-mediated autoimmune and inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)1679-1687
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Fas Ligand Protein
B-Lymphocytes
T-Lymphocytes
Antigens
Autoimmune Diseases
Delayed Hypersensitivity
Intravenous Injections
Clone Cells
Lymph Nodes
Lymphocytes
Apoptosis
Therapeutics

Keywords

  • Antigen-presenting cell
  • B cell
  • Delayed-type hypersensitivity
  • Fas ligand
  • Immunosuppression

ASJC Scopus subject areas

  • Immunology

Cite this

B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo. / Kosiewicz, Michele M.; Krishnan, Anasuya; Worthington, Mark T.; Matriano, James A.; Ross, William G.

In: European Journal of Immunology, Vol. 32, No. 6, 2002, p. 1679-1687.

Research output: Contribution to journalArticle

Kosiewicz, Michele M. ; Krishnan, Anasuya ; Worthington, Mark T. ; Matriano, James A. ; Ross, William G. / B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo. In: European Journal of Immunology. 2002 ; Vol. 32, No. 6. pp. 1679-1687.
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