J Mol Med (2005) 83: 752–763 DOI 10.1007/s00109-005-0675-z REVIEW Fabrizio Vianello . Ivona T. Olszak . Mark C. Poznansky Fugetaxis: active movement of leukocytes away from a chemokinetic agent Received: 14 June 2004 / Accepted: 3 March 2005 / Published online: 3 September 2005 # Springer-Verlag 2005 Abstract Chemotaxis or active movement of leukocytes toward a stimulus has been shown to occur in response to chemokinetic agents including members of the recently identified superfamily of proteins called chemokines. Leu- kocyte chemotaxis is thought to play a central role in a wide range of physiological and pathological processes including the homing of immune cells to lymph nodes and the accumulation of these cells at sites of tissue injury and pathogen or antigen challenge. We have recently identified a novel biological mechanism, which we term fugetaxis (fugere, to flee from; taxis, movement) or chemorepulsion, which describes the active movement of leukocytes away from chemokinetic agents including the chemokine, stro- mal cell derived factor-1, and the HIV-1 envelope protein, gp120. In this article, we review the evidence that supports the observation that leukocyte fugetaxis occurs in vitro and in vivo and suggestions that this novel mechanism can be exploited to modulate the immune response. We propose that leukocyte fugetaxis plays a critical role in both phys- iological and pathological processes in which leukocytes are either excluded or actively repelled from specific sites in vivo including thymic emigration, the establishment of immune privileged sites and immune evasion by viruses and cancer. We believe that current data support the thesis that a greater understanding of leukocyte fugetaxis will lead to the development of novel therapeutic approaches for a wide range of human diseases. Keywords Fugetaxis . T cells . Immune response . T cell development . Immune evasion Introduction: eukaryotic cell migration toward and away from a chemokinetic agent Active movement of leukocytes toward a site of antigen challenge, infection, or tissue injury is a central component of the establishment of both inflammatory and immune responses [1–4]. The movement of cells toward or up a IVONA OLSZAK obtained her B.Sc. degree from University of Massachusetts and Mount Holyoke College. She subsequently worked at the Department of Pathology and at the Partners AIDS Research Center at Massachusetts Gen- eral Hospital, where she studied novel factors controlling im- mune cell migration. While at MGH, she made significant contributions to the exploration of leukocyte fugetaxis. She subsequently obtained an MBA from Northeastern University and currently manages the core laboratory facilities at the Dana Farber Cancer Institute and the Dana Farber/Harvard Cancer Center. MARK C. POZNANSKY received his medical degree from Edinburgh University and his Ph.D. from Cambridge University in the UK. He was awarded a Harkness Fellowship and pursued postdoctoral work in HIV/AIDS research at the Dana Farber Cancer Institute in Boston and at St. Mary’ s Hos- pital/Imperial College in London. He currently has a laboratory at Massachusetts General Hospital in Boston which focuses on the molecular mechanism of leukocyte direc- tional decision making and the role that leukocyte fugetaxis plays in physiological processes including thymic emigration and the pathogenesis of HIV/ AIDS and cancer. F. Vianello . I. T. Olszak . M. C. Poznansky (*) Partners AIDS Research Center, Massachusetts General Hospital (East), Bldg. 149, 13th Street, Charlestown Navy Yard, MA 02129, USA e-mail: mpoznansky@partners.org Tel.: +1-617-7246375 Fax: +1-617-7264693