Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection

Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT) criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection. 1. Introduction Bronchus-associated lymphoid tissue (BALT) presence has been described in many animal species and in normal human lung tissue. BALT consists of follicular lymphoid aggregates within the mucosa of the bronchial tree [1]. BALT plays a role in local host defense similar to gut associated lymphoid tissue and tonsils. In addition, it is involved in antigen distribution and processing between the lung tissue and the mediastinal lymph nodes. In humans with inflammatory disease such as chronic obstructive pulmonary disease (COPD) and rheumatologic lung diseases the presence and number of BALT increases as the severity of disease worsens [2, 3]. Specifically there are an increased number of lymphoid follicles as the degree of airflow obstruction worsens in COPD [2]. In diseases such as rheumatoid lung, the presence of well-organized BALT is associated with the local expression of cytokines and enzymes that play a role in the pathobiology of autoimmune lung diseases [3]. BALT is often seen on transbronchial biopsy (TBBx) specimens in lung transplantation; however, the significance of its presence is not well understood. In rat transplantation models,