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Regular Articles |
From the Laboratory of Immunology and Vascular Biology,*
Department of Pathology, the Department of Microbiology and
Immunology,
the Department of
Surgery,¶
and the Division of Immunology and
Rheumatology,||
Stanford University School of Medicine,
Stanford, California; Center for Molecular Biology and
Medicine,
Veterans Affairs Palo Alto Health
Care System, Palo Alto, California; Millennium Pharmaceuticals,
Inc.,
Cambridge, Massachusetts; Division of
Respiratory Medicine,**
Institute for Lung
Health, Leicester University Medical School, Leicester, United Kingdom;
and the Joint Program in Transfusion
Medicine,
Children’s Hospital,
and the Department of Pathology, Harvard Medical School,
Boston, Massachusetts
Differential expression of adhesion molecules and chemokine
receptors has been useful for identification of peripheral blood memory
lymphocyte subsets with distinct tissue and microenvironmental
tropisms. Expression of CCR4 by circulating memory CD4+
lymphocytes is associated with cutaneous and other systemic populations
while expression of CCR9 is associated with a small intestine-homing
subset. CCR5 and CXCR3 are also expressed by discrete memory
CD4+ populations in blood, as well as by
tissue-infiltrating lymphocytes from a number of sites. To characterize
the similarities and differences among tissue-infiltrating
lymphocytes, and to shed light on the specialization of
lymphocyte subsets that mediate inflammation and immune surveillance in
particular tissues, we have examined the expression of
CCR4, CXCR3, and CCR5 on CD4+ lymphocytes
directly isolated from a wide variety of normal and inflamed tissues.
Extra-lymphoid tissues contained only memory lymphocytes, many
of which were activated (CD69+). As predicted by classical
studies, skin lymphocytes were enriched in CLA expression
whereas intestinal lymphocytes were enriched in
4ß7 expression. CCR4 was expressed at high
levels by skin-infiltrating lymphocytes, at lower levels by
lung and synovial fluid lymphocytes, but never by intestinal
lymphocytes. Only the high CCR4 levels characteristic of skin
lymphocytes were associated with robust chemotactic and adhesive
responses to TARC, consistent with a selective role for CCR4 in
skin lymphocyte homing. In contrast, CXCR3 and CCR5 were
present on the majority of lymphocytes from each non-lymphoid tissue
examined, suggesting that these receptors are unlikely to
determine tissue specificity, but rather, may play a
wider role in tissue inflammation.
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P. Gao, X.-Y. Zhou, Y. Yashiro-Ohtani, Y.-F. Yang, N. Sugimoto, S. Ono, T. Nakanishi, S. Obika, T. Imanishi, T. Egawa, et al. The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3 J. Leukoc. Biol., February 1, 2003; 73(2): 273 - 280. [Abstract] [Full Text] [PDF]
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T. L. Humphreys, C. T. Schnizlein-Bick, B. P. Katz, L. A. Baldridge, A. F. Hood, R. A. Hromas, and S. M. Spinola Evolution of the Cutaneous Immune Response to Experimental Haemophilus ducreyi Infection and Its Relevance to HIV-1 Acquisition J. Immunol., December 1, 2002; 169(11): 6316 - 6323. [Abstract] [Full Text] [PDF]
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V. Szanya, J. Ermann, C. Taylor, C. Holness, and C. G. Fathman The Subpopulation of CD4+CD25+ Splenocytes That Delays Adoptive Transfer of Diabetes Expresses L-Selectin and High Levels of CCR7 J. Immunol., September 1, 2002; 169(5): 2461 - 2465. [Abstract] [Full Text] [PDF]
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