Lung transplantation affects expression of the chemokine receptor type 4 on specific T cell subsets

Paantjens, A. W. M.; van de Graaf, E. A.; Kwakkel-van Erp, J.M.; Hoefnagel, T.; van Kessel, D. A.; van den Bosch, J. M. M.; Otten, H. G.

doi:10.1111/J.1365-2249.2011.04450.X

Title

Lung transplantation affects expression of the chemokine receptor type 4 on specific T cell subsets

Author

Paantjens, A. W. M.

van de Graaf, E. A.

Kwakkel-van Erp, J.M.

Hoefnagel, T.

van Kessel, D. A.

van den Bosch, J. M. M.

Otten, H. G.

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 centralmemory, 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.

Language

English

Source (journal)

Clinical and experimental immunology. - Oxford

Publication

Oxford : 2011

ISSN

0009-9104

DOI

10.1111/J.1365-2249.2011.04450.X

Volume/pages

166 :1 (2011) , p. 103-109