The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published 7 January 2002. doi:10.1084/jem.20011502
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© Rockefeller University Press, 0022-1007/2002/1/135/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 1, January 7, 2002 135-141

Brief Definitive Report

Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues

Daniel J. Campbell1,2 and Eugene C. Butcher1,2

1 Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
2 Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304

Address correspondence to D.J. Campbell, 154B 3801 Miranda Ave., Palo Alto, CA 94304. Phone: 650-493-5000 ext. 63132; Fax: 650-858-3986; E-mail: daniel{at}macampbell.com

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and {alpha}4ß7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate {alpha}4ß7, while those responding to antigen in intestinal lymph nodes selectively express high levels of {alpha}4ß7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

Key Words: T cell • homing • chemokine • adhesion • lymph node


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