The significance of bronchus-associated lymphoid tissue in human lung transplantation: is there an association with acute and chronic rejection?
BACKGROUND
In animal models of acute rejection in lung allografts, bronchus-associated lymphoid tissue (BALT) plays a major role in the induction and persistence of the alloreactive response. We undertook a study of the clinical and histologic associations with BALT identified on transbronchial biopsy in human lung allograft recipients.


METHODS
Transbronchial biopsies of patients receiving single lung, double lung, and combined heart-lung transplantation from 1984 to 1997 at the University of Pittsburgh Medical Center were reviewed. Seventy-seven patients had transbronchial biopsies demonstrating BALT. We examined all pathologic reports and slides, and graded rejection utilizing the Revised Working Formulation for the Classification of Pulmonary Allograft Rejection. Twenty-nine of 77 patients were selected at random to evaluate the distribution of BALT lymphocyte subsets immunohistochemically.


RESULTS
There was no relationship between native disease or the transplant procedure and the identification of BALT. BALT was found from 9 days to 2431 days after transplant (average: 440 days; median: 157 days) in association with clinically insignificant acute cellular rejection (A0, A1) in 75% of cases. Bronchiolitis obliterans developed in 29% of patients with a BALT-positive biopsy, a percentage not different from that of our overall lung transplant population. Immunohistochemical examination of BALT showed helper T cells predominated over cytotoxic T cells in zones surrounding B cell-rich follicular center cells.


CONCLUSIONS
The association of BALT with high-grade acute cellular rejection and with the development of bronchiolitis obliterans could not be confirmed in human lung allografts. BALT most often accompanied A0 or A1 rejection. This raises the possibility that the presence of BALT on transbronchial biopsy may be part of the evolution of immunologic tolerance in human pulmonary allografts.
Department of Pathology, University of Pittsburgh Medical Center-Presbyterian University Hospital, Pennsylvania 15213, USA.
T
T
Hasegawa
A
A
Iacono
S A
SA
Yousem
D000208:Acute Disease; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000145:classification / Q000276:immunology / Q000473:pathology*; D016041:Heart-Lung Transplantation / Q000276:immunology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology
D007166:Immunosuppressive Agents