Upregulation of CD40, CD80, CD83 or CD86 on alveolar macrophages after 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.
Nicod
Laurent P
LP
Pulmonary Division, University Hospital of Bern, Switzerland. laurent.nicod@insel.ch
Joudrier
Sylvia
S
Isler
Patrick
P
Spiliopoulos
Anastase
A
Pache
Jean-Claude
JC
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D051940:B7-2 Antigen / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019013:CD40 Antigens / Q000032:analysis*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis*; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000166:cytology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D011379:Prognosis; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014181:Transplantation Immunology / Q000502:physiology*; D015854:Up-Regulation; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen