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Immunobiology of Organ Transplantation pp 329–341Cite as

Cytotoxic T Lymphocytes: Mechanism of Action and Role in Allograft Rejection

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Abstract

The discovery of cytotoxic T lymphocytes (CTL) emerged from attempts to understand the basis for tumor immunity, delayed-type hypersensitivity (DTH) reactions, and especially allograft rejection. These phenomena had the hallmarks of immune reactions, such as the involvement of lymphoid cells, specificity, and memory, but they could not be fully accounted for by antibody. Evidence suggesting direct killing of specifically recognized allogeneic target cells byin vivosensitized lymphocytes was first provided by Weaver in 19551. Weaver found that when transplants were placed inside diffusion chambers permeable to large molecules but not to cells, they were not rejected when the chambers were implanted into naive or primed allogeneic animals. This was consistent with previous evidence that antibodies from immune serum were not sufficient for graft rejection2. But immune spleen cells were. If spleen cells from a mouse that had previously rejected a graft of the same type were placed into the same diffusion chamber as the secondary transplant, the transplant within the chamber was rapidly destroyed. Hence, Weaver concluded that transplant rejection was caused by contact-mediated destruction of graft cells induced by immune cells, rather than soluble molecules, a suggestion made even earlier by Kidd in 19503based on detailed histopathology of graft rejectionin vivo.

A major transition in the study of lymphocyte-mediated cytotoxicity came about in 1960, with the report by Andre Govaertz in 19604that thoracic duct lymphocytes isolated from dogs after rejection of a renal allograft were capable of destroyingin vitromonolayer cultures of kidney cells obtained from the donor’s contralateral kidney, but not kidney cells from an unrelated donor. This finding showed that the attacking cells were part of a recirculating population of lymphocytes. At the time of this discovery of killer lymphocytes, the existence of distinct T- and B-lymphocyte subpopulations was not yet appreciated. But once these subsets were demonstrated, and a marker found for T cells—the so-called theta 9 (for thymus) antigen—the identity of killer cells within T lymphocytes was established5.

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Authors and Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Gideon Berke

  2. Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA

    William R. Clark

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  1. Gideon Berke
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Editors and Affiliations

  1. Microbiology and Immunobiology, Division of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, Indiana

    David S. Wilkes M.D. (Calvin H. English Professor of Medicine) (Calvin H. English Professor of Medicine)

  2. Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, Wisconsin

    William J. Burlingham Ph.D. (Associate Professor) (Associate Professor)

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© 2004 Springer Science+Business Media New York

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Berke, G., Clark, W.R. (2004). Cytotoxic T Lymphocytes: Mechanism of Action and Role in Allograft Rejection. In: Wilkes, D.S., Burlingham, W.J. (eds) Immunobiology of Organ Transplantation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8999-4_18

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  • DOI: https://doi.org/10.1007/978-1-4419-8999-4_18

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  • Print ISBN: 978-1-4613-4754-5

  • Online ISBN: 978-1-4419-8999-4

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