Lymphodepletional strategies in transplantation.

Published

Journal Article (Review)

Because lymphocytes were shown to mediate transplant rejection, their depletion has been studied as a mechanism of preventing rejection and perhaps inducing immunologic tolerance. Agents that profoundly deplete lymphocytes have included monoclonal antibodies, cytotoxic drugs, and radiation. We have studied several such agents but focused on antibodies that deplete not only peripheral blood lymphocytes, but also lymph node lymphocytes. Depletion of lymph node T lymphocytes appears to permit peripheral tolerance at least for T cells in animal models. Nevertheless, B-cell responses may be resistant to such approaches, and T memory cells are likewise relatively resistant to depleting antibodies. We review the experimental and clinical approaches to depletion strategies and outline some of the pitfalls of depletion, such as limitations of currently available agents, duration of tolerance, infection, and malignancy. It is notable that most tolerogenic strategies that have been attempted experimentally and clinically include depleting agents even when they are not named as the underlying strategy. Thus, there is an implicitly acknowledged role for reducing the precursor frequency of donor antigen-specific lymphocytes when approaching the daunting goal of transplant tolerance.

Full Text

Duke Authors

Cited Authors

  • Page, E; Kwun, J; Oh, B; Knechtle, S

Published Date

  • July 2013

Published In

Volume / Issue

  • 3 / 7

PubMed ID

  • 23818516

Pubmed Central ID

  • 23818516

Electronic International Standard Serial Number (EISSN)

  • 2157-1422

International Standard Serial Number (ISSN)

  • 2157-1422

Digital Object Identifier (DOI)

  • 10.1101/cshperspect.a015511

Language

  • eng