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Science 305 (5681): 193-

Copyright © 2004 by the American Association for the Advancement of Science

Two Sides of a Coin

Stephen J. Simpson and Eliot Marshall

Putting Tolerance to the Test
Viewpoints and Reviews
Immunotherapy: Bewitched, Bothered, and Bewildered No More
R. M. Steinman and I. Mellman
Cancer Immunotherapy: A Treatment for the Masses
J. N. Blattman and P. D. Greenberg
Therapeutic Vaccines for Chronic Infections
B. Autran et al.
Exploiting Tolerance Processes in Transplantation
H. Waldmann and S. Cobbold
Immune Therapy for Autoimmune Diseases
L. Steinman
See related Editorial, News story, and Science's SAGE KE and STKE material.
When Brutus and his conspirators plotted to assassinate Julius Caesar on 15 March 44 B.C.E., they considered it an act of loyalty to the republic; yet at the same time it was a betrayal of the leader they had sworn to protect. The immune system also presents two faces: On the one hand, it works to protect us by fighting infection and malignancy; while on the other, it can prove treacherous, attacking tissues and cells of the body to produce debilitating and even fatal autoimmune diseases.

For autoimmune conditions, immunotherapy offers the potential to limit the damage done by reining in the disease-causing cells. On the opposite side of the balance, clinicians are deploying therapeutic interventions to augment the immune system in its struggle against cancer and chronic viral infections. In this special issue, we've invited experts to review progress in immunotherapy in a range of clinical and experimental settings.

Steinman and Mellman (p. 197) set the scene with their view on how basic research in immunology could best be conveyed to the clinical arena, and Blattman and Greenberg (p. 200) explore in detail how this might be achieved to treat malignancy. In many ways, clinicians face similar obstacles in tackling chronic infectious diseases such as HIV, and Autran and colleagues (p. 205) offer insights into the potential of therapeutic vaccines.

Transplantation and autoimmunity represent the flip side of the coin, and here the problem is to harness, rather than release, the natural regulatory brakes of the immune system. Waldmann and Cobbold (p. 209) consider how these regulatory processes might be integrated to achieve acceptance of transplanted organs. Finally, Steinman (p. 212) discusses ways in which immunotherapy is being used to target autoimmunue diseases such as multiple sclerosis.

Figure 1
A coin struck by Brutus in 43/2 B.C.E. refers to his assassination of Caesar. On one side is the head of Brutus and on the other is the symbol of two daggers and a helmet, with the inscription "Eid Mar" (the Ides of March).


One of the most ambitious clinical projects to date is the U.S. Immune Tolerance Network, which is testing streamlined drug treatments for autoimmune disorders and organ transplantation, described in a News report by Couzin on page 194. On page 170 of the News Focus section, Wickelgren reports on controversial efforts to calm overactive immune systems with a cocktail of parasitic worms.

Science Online's STKE and SAGE KE ( continue these themes. In STKE, Engleman et al. consider how robust immunity to tumors might be stimulated via dendritic cell activation. Heissmeyer and Rao discuss intracellular pathways regulating T cell tolerance, and Olszewski and Grossbard overview the ways in which a successful mode of antibody immunotherapy achieves its results. In SAGE KE, a Perspective by P. L. McGeer and E. McGeer considers the challenges of vaccination in treating Alzheimer's disease, and a feature story by Leslie explores why vaccines often fail in the elderly--and what scientists are doing to boost their potency.

The concepts behind immunotherapy have brought us to an exciting new frontier. The expectations now are that resolution of the diseases discussed in this issue will fall increasingly under our control, rather than appearing to be left to the simple toss of a coin.

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