title: Lung transplantation affects expression of the chemokine receptor type 4 on specific T cell subsets.
abstract: Alloreactive T cells that infiltrate the graft after lung transplantation (LTx) play a role in chronic rejection. Chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and monocyte chemotactic protein-1 (MCP-1) are produced locally in the lung and attract T cells via chemokine receptor 4 (CCR4). In a TARC gradient, cells expressing CCR4(++) migrate more efficiently than CCR4(+) -expressing cells. In this study, we compared the CCR4 expression of T cells in blood from 20 lung transplant recipients to healthy controls. We then examined whether CCR4 expression is associated with the occurrence of chronic rejection. The CCR4(++) expression was decreased on CD4 T cells from LTx patients (P < 0·0001) when compared to healthy controls. The analysis of CD4 T cell subsets showed that this decrease was present on central memory, effector memory and terminally differentiated T cells (P = 0·0007, P < 0·0001 and P = 0·05, respectively), while a trend was found for naive CD4 T cells (P = 0·06). Also, the expression of CCR4(+) on regulatory T cells (T(regs) ) was decreased in LTx patients when compared to healthy controls (P = 0·02). Interestingly, the CCR4(++) expression on CD4 effector memory T cells was decreased in patients developing chronic rejection sometimes more than a year before the clinical diagnosis when compared to patients who did not (P = 0·04). The analysis of CD8 T cell subsets only showed the CCR4(+) expression to be increased significantly on effector memory and terminally differentiated CD8 T cells (P = 0·02, P = 0·03, respectively) in LTx patients, but no relation was found in chronic rejection. In conclusion, the expression of CCR4 on T cell subsets was altered after LTx and appears to be related to chronic rejection.
authors.affiliation: Departments of Immunology Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. a.paantjens@umcutrecht.nl
authors.forename: A W M
authors.initials: AW
authors.lastname: Paantjens
authors.forename: E A
authors.initials: EA
authors.lastname: van de Graaf
authors.forename: J M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.forename: T
authors.initials: T
authors.lastname: Hoefnagel
authors.forename: D A
authors.initials: DA
authors.lastname: van Kessel
authors.forename: J M M
authors.initials: JM
authors.lastname: van den Bosch
authors.forename: H G
authors.initials: HG
authors.lastname: Otten
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001989:Bronchiolitis Obliterans / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000096:biosynthesis / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000276:immunology; D054422:Chemokine CCL22 / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; C106230:CCL17 protein, human; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D054398:Receptors, CCR4