Expression of chemokine receptors by lung T cells from normal and asthmatic subjects.
The lung is an important tertiary lymphoid organ with constant trafficking of T cells through the lung in both health and disease. T cell migration is controlled by a combination of adhesion receptors and chemokines expressed on vascular endothelium and in the tissue, often in an organ-specific manner. This leads to selective accumulation of different T cell subsets, a process called lymphocyte homing. There is evidence for a distinct lung-homing pathway, but no specific lung-homing receptors have been described. We analyzed the chemokine receptor profile of lung T cells to determine the extent to which lung T cells shared homing pathways with other organs such as the gut and skin. In addition, we compared expression of receptors in normal and asthmatic individuals to determine whether different pathways were used in health and disease. We observed that lung T cells expressed a profile of chemokine and adhesion receptors distinct from that of gut- and skin-homing T cells although no chemokine receptor specific for the lung was found. In particular, lung T cells expressed CCR5 and CXCR3, but not CCR9 or cutaneous lymphocyte Ag, and only low levels of CCR4 and alpha(4)beta(7). No differences were observed between lung T cells from normal vs asthmatic subjects. This study provides added support for the concept of a lung-homing pathway separate from other mucosal organs such as the gut and suggests that the chemokine pathways that control T cell migration in normal homeostasis and Th2-type inflammatory responses are similar.
Campbell
J J
JJ
Institute for Lung Health and Division of Respiratory Medicine, Leicester University School of Medicine, Leicester, United Kingdom.
Brightling
C E
CE
Symon
F A
FA
Qin
S
S
Murphy
K E
KE
Hodge
M
M
Andrew
D P
DP
Wu
L
L
Butcher
E C
EC
Wardlaw
A J
AJ
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002469:Cell Separation; D006801:Humans; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011013:Pneumonectomy; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing