CXCR6 is expressed on T cells in both T helper type 1 (Th1) inflammation and allergen-induced Th2 lung inflammation but is only a weak mediator of chemotaxis.
Numerous chemokine receptors are increased in number on T cells in inflamed tissues. Our objective was to examine CXCR6 expression on lymphocytes during immune and inflammatory reactions and its potential for mediating T-cell recruitment. The cDNA for rat CXCR6 was cloned and monoclonal antibodies (mAbs) to CXCR6 were developed. CXCR6 was present on 4-6% of CD4 and CD8 T cells in blood, normal lymph nodes (LNs) and the spleen, primarily on memory T cells. In vitro antigen re-stimulation of LN T cells from animals with autoimmune arthritis and experimental autoimmune encephalomyelitis (EAE) increased the proportion of CXCR6(+) T cells to 35-50% and anti-T-cell receptor (TCR) activation to 60-80%. In vivo, after antigen challenge of LNs there was only a small increase in CXCR6(+) T cells on the lymphoblasts in the LNs, and a much higher percentage of T cells were CXCR6(+) in virus-induced peritoneal exudates (approximately 47%) and in allergen-induced lung inflammation (33%). Chemotaxis of CXCR6-expressing inflammatory T cells to CXCL16 was poor, but that to CXCL10 was robust. We conclude that few T cells in normal and antigen-challenged LNs are CXCR6(+), whereas a high proportion of in vitro activated T cells and T cells from inflammatory sites are CXCR6(+), but these cells migrate poorly to CXCL16. This suggests that CXCR6 may contribute to T-cell positioning and activation, rather than recruitment. CXCR6 is also expressed on T cells not only in T helper type 1 (Th1) inflammation (arthritis and EAE) but also, as shown here, in Th2 inflammation, where it is increased after allergen challenge.
Latta
Markus
M
Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
Mohan
Karkada
K
Issekutz
Thomas B
TB
D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology; D016466:CHO Cells; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D010538:Peritonitis / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; C522202:CXCR6 protein, rat; D018076:DNA, Complementary; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine