Regulatory and Effector Cell Disequilibrium in Patients with Acute Cellular Rejection and Chronic Lung Allograft Dysfunction after Lung Transplantation: Comparison of Peripheral and Alveolar Distribution
Laura Bergantini,
Miriana d’Alessandro,
Elda De Vita,
Felice Perillo,
Antonella Fossi,
Luca Luzzi,
Piero Paladini,
Anna Perrone,
Paola Rottoli,
Piersante Sestini,
Elena Bargagli,
David Bennett
Affiliations
Laura Bergantini
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Miriana d’Alessandro
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Elda De Vita
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Felice Perillo
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Antonella Fossi
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Luca Luzzi
Thoracic Surgery Unit, Department of Medicine, Surgery and Neuroscences, Siena University Hospital, 53100 Siena, Italy
Piero Paladini
Thoracic Surgery Unit, Department of Medicine, Surgery and Neuroscences, Siena University Hospital, 53100 Siena, Italy
Anna Perrone
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Paola Rottoli
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Piersante Sestini
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Elena Bargagli
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
David Bennett
Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University, 53100 Siena, Italy
Background: The immune mechanisms occurring during acute rejection (AR) and chronic lung allograft dysfunction are a challenge for research and the balance between effector and regulatory cells has not been defined completely. In this study, we aimed to elucidate the interaction of effector cells, mainly Th17, Th1 and Th2, and regulatory cells including (CD4+CD25+CD127low/−) T reg cells and phenotypes of B regs, CD19+CD24hiCD38hi, CD19+CD24hiCD27hi and CD19+CD5+CD1d+. Methods: Bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMCs) from stable lung transplanted (LTx )subjects (n = 4), AR patients (n = 6) and bronchiolitis obliterans syndrome (BOS) (n = 6) were collected at the same time. Cellular subsets were detected through flow cytometry. Results: A predominance of Th17 cells subtypes in the PBMCs and BAL and a depletion of Tregs, that resulted in decrease Treg/Th17 ratio, was observed in the AR group. CD19+CD24hiCD38hi Bregs resulted increased in BAL of AR patients. Th1 cells predominance and a reduction of Tregs cells was observed in BAL from AR patients. Moreover, multivariate analysis showed interdependences within studied variables revealing that effector cells and regulatory cells can effectively discriminate patients’ immunological status. Conclusions: In AR, BOS and stable lung transplant, regulatory and effector cells clearly demonstrated different pathways of activation. Understanding of the balance of T cells and T and B regulatory cells can offers insights into rejection.