Specificity and Plasticity of Memory Lymphocyte Migration

CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA [email protected]

1 Introduction 84

2 Homing of Naive T and B Cells 85

3 Migration of Antigen-Experienced Lymphocytes 92

3.1 Homing of Effector/Memory T Cells 92

3.2 Tissue-Specific Homing Receptors: "Zip Codes" Shape Immune Responses 93

3.3 Homing of Antibody-Secreting Cells (ASC) 97

4 Teaching Lymphocytes Where to Go:

Mechanisms Driving "Gut" Versus "Peripheral" Homing 99

5 Modulation of Lymphocyte Homing for Therapeutic Purposes 103

6 Re-educating Tissue-Specific T Cells—

A New Platform for Immunomodulation? 105

7 Future Directions 107

References 109

Abstract To exert immunological activity, T and B cells must leave the blood and enter different extravascular compartments in the body. An essential step in this process is their adhesion to microvascular endothelium and subsequent diapedesis into a target tissue. Naive and effector/memory T and B cells possess distinct repertoires of traffic molecules that restrict their ability to interact with specialized microvessels in different anatomic compartments and thus exhibit distinct patterns of migration. In addition, antigen-experienced lymphocytes are subdivided into different subsets based on their expression of characteristic sets of adhesion receptors that favor their accumulation in certain target organs, such as the skin and the gut. This article focuses on recent discoveries that have broadened our understanding of the "imprinting" mechanisms responsible for the generation of tissue-specific effector/memory lymphocytes, especially in the intestine. We discuss how gut-specific homing is acquired, maintained, and modulated and how these mechanisms might be harnessed to develop improved vaccine protocols and treatments for intestinal autoimmune diseases.

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