Anti-CD3∈F(ab′) 2 Fragments Inhibit T Cell Expansion in Vivo during Graft-Versus-Host Disease or the Primary Immune Response to Nominal Antigen

Bruce R. Blazar, Marc K. Jenkins, Patricia A. Taylor, Jennifer White, Angela Panoskaltsis-Mortari, Robert Korngold, Daniel A. Vallera

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


This study was undertaken to distinguish between several mechanisms responsible for graft-vs-host disease (GVHD) protection in anti-CD3∈F(ab′)2 fragment (Fr)-treated recipients: TCR down-modulation, deletion, failure of expansion, or anergy induction. To quantify alloreactive T cell expansion and function, thoracic duct lymphocytes (TDL) were analyzed. Sixfold fewer donor TDL T cells were recoverable from anti-CD3∈F(ab′)2 Fr as compared with irrelevant F(ab′)2 Fr-treated recipients at the time of peak T cell expansion in vivo. Kinetic analysis revealed that donor T cell expansion was inhibited and not simply delayed by anti-CD3∈F(ab′)2 Fr. Similar proportions of TDL T cells in irrelevant and anti-CD3∈F(ab′)2 Fr were undergoing apoptosis. Although TCR modulation was observed, donor TDL T cells had intact anti-host alloresponses as compared with irrelevant F(ab′)2 Fr-treated recipients. Because donor CD4+ T cells are primarily responsible for GVHD in this model, an adoptive transfer system was used in which the function and kinetics of expansion of OVA-specific CD4+ TCR transgenic cells could be physically tracked. Relevant Fr severely blunted CD4+ TCR transgenic T cell clonal expansion after OVA administration. Nonviable transgenic and nontransgenic T cells were proportionally similar in OVA-pulsed recipients, regardless of whether relevant or irrelevant F(ab′)2 Fr were given. After discontinuing Fr, transgenic T cells were found to have intact in vitro OVA-specific responses. Our current and previous results suggest that reduced donor T cell expansion and T cell depletion both contribute to GVHD protection by anti-CD3∈F(ab′)2 Fr. These data have implications for designing therapeutic approaches directed toward TCR targeting in humans.

Original languageEnglish (US)
Pages (from-to)5821-5833
Number of pages13
JournalJournal of Immunology
Issue number12
StatePublished - Dec 15 1997


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