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CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis.

Publication ,  Journal Article
Blair, PJ; Riley, JL; Harlan, DM; Abe, R; Tadaki, DK; Hoffmann, SC; White, L; Francomano, T; Perfetto, SJ; Kirk, AD; June, CH
Published in: J Exp Med
February 21, 2000

Signals generated through CD28-B7 and CD40 ligand (CD40L)-CD40 interactions have been shown to be crucial for the induction of long-term allograft survivability. We have recently demonstrated that humanized anti-CD40L (hu5C8) prevents rejection of mismatched renal allografts in primates. To investigate potential mechanisms of CD40L-induced allograft acceptance, we coimmobilized hu5C8 with suboptimal amounts of anti-CD3 to stimulate CD4(+) T cells. We now report that anti-CD3/CD40L costimulation results in CD28-independent activation and subsequent deletion of resting T cells. Coligation of CD3 and CD40L increased expression of CD69, CD25, and CD54 on CD4(+) T cells. We also found that costimulation with anti-CD3/CD40L resulted in enhanced production of interleukin (IL)-10, interferon gamma, and tumor necrosis factor alpha but not IL-2 or IL-6. Interestingly, after several days, anti-CD3/CD40L-mediated activation was followed by apoptosis in a significant population of cells. Consistent with that observation, anti-CD3/CD40L did not enhance the antiapoptotic proteins Bcl-2 and Bcl-xL. Further, the addition of CD28 at 24 h failed to rescue those cells induced to die after costimulation with anti-CD3/CD40L. Together, these data suggest that the graft-sparing effect of hu5C8 in vivo may result in part from early and direct effects on CD4(+) T cells, including a vigorous induction of immunomodulatory cytokines and/or apoptosis of allograft-specific T cells.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

February 21, 2000

Volume

191

Issue

4

Start / End Page

651 / 660

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Membrane Glycoproteins
  • Major Histocompatibility Complex
  • Lymphocyte Activation
  • Interleukins
  • Interferon-gamma
 

Citation

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Blair, P. J., Riley, J. L., Harlan, D. M., Abe, R., Tadaki, D. K., Hoffmann, S. C., … June, C. H. (2000). CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. J Exp Med, 191(4), 651–660. https://doi.org/10.1084/jem.191.4.651
Blair, P. J., J. L. Riley, D. M. Harlan, R. Abe, D. K. Tadaki, S. C. Hoffmann, L. White, et al. “CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis.J Exp Med 191, no. 4 (February 21, 2000): 651–60. https://doi.org/10.1084/jem.191.4.651.
Blair PJ, Riley JL, Harlan DM, Abe R, Tadaki DK, Hoffmann SC, et al. CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. J Exp Med. 2000 Feb 21;191(4):651–60.
Blair, P. J., et al. “CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis.J Exp Med, vol. 191, no. 4, Feb. 2000, pp. 651–60. Pubmed, doi:10.1084/jem.191.4.651.
Blair PJ, Riley JL, Harlan DM, Abe R, Tadaki DK, Hoffmann SC, White L, Francomano T, Perfetto SJ, Kirk AD, June CH. CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. J Exp Med. 2000 Feb 21;191(4):651–660.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

February 21, 2000

Volume

191

Issue

4

Start / End Page

651 / 660

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Membrane Glycoproteins
  • Major Histocompatibility Complex
  • Lymphocyte Activation
  • Interleukins
  • Interferon-gamma