HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

Invited Review

Differential signaling through the T cell receptor: from biochemistry to transplantation tolerance

J. Madrenas and A.I. Lazarovits

The John P. Robarts Research Institute, and the Departments of Microbiology and Immunology and Medicine, The University of Western Ontario, London, Ontario, Canada

Offprint requests to: Joaquín Madrenas, The John P. Robarts Research Institute, Department of Microbiology and Immunology, and Medicine, The University of Western Ontario, London, Ontario, Canada N6A 5K8

Summary. Recent advances in our understanding of the structural nature of T cell activation and signal trans-duction from the T cell receptor for antigen make possible the development of new tolerogenic strategies. Here, we summarize the evidence supporting a critical role for the co-receptor molecule (CD4 or CD8) and CD45 in determining the pattern of T cell receptor-mediated signaling. The consequences of this differential signaling can range from T cell proliferation and cytokine production to the establishment of a state of proliferative unresponsiveness known as T cell anergy. Inducing T cell anergy can be an alternative approach for the establishment of transplantation tolerance. Histol Histopathol 13, 221-229 (1998)

Key words: Signal transduction, Transplantation, T cell tolerance