Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes.
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 alpha(4)beta(7) 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.
Kunkel
Eric J
EJ
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Boisvert
Judie
J
Murphy
Kristine
K
Vierra
Mark A
MA
Genovese
Mark C
MC
Wardlaw
Andrew J
AJ
Greenberg
Harry B
HB
Hodge
Martin R
MR
Wu
Lijun
L
Butcher
Eugene C
EC
Campbell
James J
JJ
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015704:CD4 Antigens / Q000032:analysis; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016023:Integrins / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000378:metabolism*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C515354:CCR4 protein, human; D015704:CD4 Antigens; C063419:CTAGE1 protein, human; C515187:CXCR3 protein, human; D016023:Integrins; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C071777:integrin alpha4beta7