Interleukin-4 promotes human CD8 T cell expression of CCR7.
Despite strong evidence supporting a pathway of human T cell differentiation characterized by changes in the expression of CCR7, CD28, CD27 and CD62L, few studies have addressed the mechanisms of pathway regulation. Cutaneous lymphocyte-associated antigen (CLA)-positive skin-homing CD8(+) T cells expressed significantly elevated levels of activation markers compared with CLA(-) CD8(+) T cells in individuals (n = 27) with cutaneous atopic disease. Despite such an activated phenotype, CLA(+) T cells expressed significantly higher levels of CCR7 than a CLA(-) T cell subset. Interleukin (IL)-4 was found to dramatically promote CCR7 expression by antigen-specific CD8(+) cells. Furthermore, skin-homing CD8(+) T cells from individuals with severe disease produced significantly less IL-10 than those derived from mildly affected atopic subjects. Thus in a T-helper 2 dominated disease, tissue-specific CD8(+) T cells show altered CCR7 expression and cytokine production, which may contribute to continued lymph node homing, antigen presentation and disease. IL-4 promotes expression of CCR7, a marker linked to existing models of CD8(+) T cell differentiation.
Seneviratne
Suranjith L
SL
MRC Human Immunology Unit and University of Oxford, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom.
Black
Antony P
AP
Jones
Louise
L
di Gleria
Kati
K
Bailey
Abigail S
AS
Ogg
Graham S
GS
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C515370:CCR7 protein, human; D016207:Cytokines; D007378:Interleukins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015847:Interleukin-4