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Long‐Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor‐Specific Immune Responses
Author(s) -
Nayak D. K.,
Zhou F.,
Xu M.,
Huang J.,
Tsuji M.,
Hachem R.,
Mohanakumar T.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13819
Subject(s) - medicine , lung transplantation , bronchoalveolar lavage , immunology , immune system , lung , adoptive cell transfer , transplantation , human leukocyte antigen , extrinsic allergic alveolitis , antigen , pathology , t cell
Steady‐state alveolar macrophages ( AM s) are long‐lived lung‐resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation ( LT x). Our goal was to examine donor AM longevity and evaluate whether AM s of recipient origin seed the transplanted lungs. Origin of AM s was accessed using donor–recipient HLA mismatches. We demonstrate that 94–100% of AM s present in bronchoalveolar lavage ( BAL ) were donor derived and, importantly, AM s of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post‐ LT x revealed that the majority of AM s (>87%) was donor derived. Elicitation of de novo donor‐specific antibody ( DSA ) is a major post‐ LT x complication and a risk factor for development of chronic rejection. The donor AM s responded to anti‐ HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AM s stimulated humoral and cellular immune responses to alloantigen and lung‐associated self‐antigens and led to bronchiolar obstruction. Therefore, donor‐derived AM s play an essential role in the DSA ‐induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs.