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

Summary 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.