BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T cells. The question raised is about the potential changes in phenotypes after lung transplantation, particularly during acute rejection episodes. METHODS: The present study analyzed the phenotype of AMs longitudinally in 45 lung transplant patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/- 2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL) assessments performed per patient (i.e., 345 BALs), simultaneously with transbronchial biopsies. Transplantation was soon followed by a progressive upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80, as well as CD83, a marker of dendritic cells, were enhanced for most AMs during Grade A2 and A3 rejection episodes. A correlation was found between expression of CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40-positive cells in the alveoli corresponded to AMs and to some dendritic cells in the basal layers of the airways. In vitro studies showed that harvested AMs with these enhanced accessory molecules remained poor stimulators of allogeneic cells, a phenomenon that may be related to the ongoing immunosuppressive treatments. CONCLUSIONS: AM phenotypes showed marked changes during early or late acute rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was further enhanced. This finding may provide clues on how to monitor the tolerance of transplanted lungs and may also provide new insights into the pathophysiology of lung transplantation.
BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T cells. The question raised is about the potential changes in phenotypes after lung transplantation, particularly during acute rejection episodes. METHODS: The present study analyzed the phenotype of AMs longitudinally in 45 lung transplant patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/- 2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL) assessments performed per patient (i.e., 345 BALs), simultaneously with transbronchial biopsies. Transplantation was soon followed by a progressive upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80, as well as CD83, a marker of dendritic cells, were enhanced for most AMs during Grade A2 and A3 rejection episodes. A correlation was found between expression of CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40-positive cells in the alveoli corresponded to AMs and to some dendritic cells in the basal layers of the airways. In vitro studies showed that harvested AMs with these enhanced accessory molecules remained poor stimulators of allogeneic cells, a phenomenon that may be related to the ongoing immunosuppressive treatments. CONCLUSIONS: AM phenotypes showed marked changes during early or late acute rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was further enhanced. This finding may provide clues on how to monitor the tolerance of transplanted lungs and may also provide new insights into the pathophysiology of lung transplantation.
Authors: Deepak K Nayak; Fangyu Zhou; Min Xu; Jing Huang; Moriya Tsuji; Jinsheng Yu; Ramsey Hachem; Andrew E Gelman; Ross M Bremner; Michael A Smith; Thalachallour Mohanakumar Journal: Sci Transl Med Date: 2017-07-12 Impact factor: 17.956
Authors: M L L Madariaga; P J Spencer; S G Michel; G M La Muraglia; M J O'Neil; E C Mannon; C Leblang; I A Rosales; R B Colvin; D H Sachs; J S Allan; J C Madsen Journal: Am J Transplant Date: 2015-10-15 Impact factor: 8.086
Authors: Christina Ehlers; Susann Schirmer; Ralph H Kehlenbach; Joachim Hauber; Jan Chemnitz Journal: Nucleic Acids Res Date: 2012-11-17 Impact factor: 16.971
Authors: Antonio Julià; Irene Bonafonte-Pardàs; Antonio Gómez; María López-Lasanta; Mireia López-Corbeto; Sergio H Martínez-Mateu; Jordi Lladós; Iván Rodríguez-Nunez; Richard M Myers; Sara Marsal Journal: Sci Rep Date: 2021-06-01 Impact factor: 4.379