Activation of T lymphocytes for adhesion and cytokine expression by toxin-conjugated anti-CD3 monoclonal antibodies.

Published

Journal Article

BACKGROUND: Immunosuppressive drugs that target T cells are useful for prolonging allograft survival. The anti-CD3 immunotoxin FN18-CRM9 has been shown to effectively prolong renal allograft survival in a rhesus monkey model of transplantation. However, immunotoxin-treated monkeys showed increased levels of inflammatory cytokines and produced antibodies to donor proteins. To better understand the role of FN18-CRM9 in the production of cytokines and anti-donor antibodies in the monkey model, we examined whether this immunotoxin elicits functional responses in T cells. METHODS: Purified normal rhesus monkey T cells (>98% purity) were incubated with immunotoxin FN18-CRM9 or the unconjugated anti-CD3 monoclonal antibodies and then examined for changes in protein tyrosine phosphorylation, adhesion to fibronectin, gene expression, and proliferation in the presence or absence of anti-CD28 monoclonal antibodies (mAb) and interleukin-2. RESULTS: Immunotoxin treatment of T cells in vitro increased protein tyrosine phosphorylation, cell adhesion to the extracellular matrix, and expression of the inflammatory cytokines interferon-gamma and tumor necrosis factor-alpha. These immunotoxin effects were similar in magnitude to those induced by the unconjugated mAb. In contrast, immunotoxin-induced T cell proliferation was markedly less than that induced by the unconjugated mAb. Interestingly, the mitogenic molecules IL-2 and anti-CD28 mAb did not prevent immunotoxin-induced inhibition of cell proliferation. CONCLUSIONS: The activation of T cells for protein phosphorylation, adhesion, and cytokine expression strongly suggests that the actions of FN18-CRM9 in vivo are not limited to the inhibition of protein synthesis.

Full Text

Duke Authors

Cited Authors

  • Hamawy, MM; Tsuchida, M; Manthei, ER; Dong, Y; Fechner, JE; Knechtle, JS

Published Date

  • September 1999

Published In

Volume / Issue

  • 68 / 5

Start / End Page

  • 693 - 698

PubMed ID

  • 10507490

Pubmed Central ID

  • 10507490

Electronic International Standard Serial Number (EISSN)

  • 1534-6080

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/00007890-199909150-00016

Language

  • eng