Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Lymphoid aggregates (LAs) have been identified within lung allografts post lung transplant (LTx). However, it remains controversial whether they represent benign lymphoid tissue or immunologically-active tertiary lymphoid organs (TLOs) and whether they participate in rejection processes, tolerance or both. We aimed to assess in detail the B and T cell component and clarify the specific molecular expression of LAs within lungs affected by chronic lung allograft dysfunction (CLAD).
*Methods: We restrospectively reviewed 46 patients who underwent a 2nd LTx due to CLAD between March 2008 and Aug 2018 at our institution. We cut sequential 5 um sections of formalin-fixed paraffin-embedded explanted lung tissue for hematoxylin-eosin, immunohistochemistry (CD21, BCL6, Lymphotoxin-beta; LTb) and immunofluorescence (CD3, CD20, PNAd) staining (Figure).
*Results: The time interval between 1st LTx and CLAD was 38.1 ± 37.9 months and time from 1st to 2nd LTx was 64.1 ± 51.7 months. We assessed 600 intra-pulmonary LAs >= 1.0×104 um2 (13.3 ± 17.2 LAs per CLAD patient). Compared with 10 healthy donor lung samples, LAs were found much more frequently in CLAD lungs (28.2 ± 38.4 x 103 n/mm2 compared to 2.5 ± 4.2 x 103 n/mm2; p=0.0003). While the sizes of LAs were similar between CLAD and healthy lungs, LAs in CLAD lungs were less dense compared to healthy lungs (7.5 ± 3.0 x 103 cells/mm2 vs. 10.6 ± 3.9 x 103 cells/mm2, p=0.0395). A reticular CD21+ follicular dendritic cell staining pattern was positive in 21.4% of CLAD lung LAs compared to 60% in healthy lungs. Within CLAD lungs, compared to CD21– LAs, the CD21+ LAs had a higher percentage of CD20+ B cells, as well as cells staining positive for LTb and BCL6, molecules involved in follicular B and T cell development. CLAD lung CD21– LAs were assessed for PNAd+ high endothelial venules (HEV), characteristic of TLOs. The majority of CLAD lung LAs were CD21–PNAd– (72.8%) and a minority CD21–PNAd+ (5.9%). CD21–PNAd+ CLAD lung TLOs contained greater proportions of CD3+ T, less CD20+ and less LTb+ cells than CD21–PNAd–. Within CD21– LAs, positive BCL6 staining correlated with more T cells.
*Conclusions: CLAD lung LAs can be broadly categorized into CD21+, CD21–PNAd+, and CD21–PNAd– LAs. The CD21+ B cell-rich LAs have strong LTb and BCL6 staining, consistent with highly-organized active lymphoid structures. CD21–PNAd+ LAs have the highest proportion of T cells. Future studies should assess whether these distinct LAs play differential roles in post-LTx immune responses.
To cite this abstract in AMA style:Miyamoto E, Juvet S, Hwang D, Keshavjee S, Martinu T. Cellular And Molecular Characteristics Of Intra-graft Lymphoid Aggregates In Chronic Lung Allograft Dysfunction [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/cellular-and-molecular-characteristics-of-intra-graft-lymphoid-aggregates-in-chronic-lung-allograft-dysfunction/. Accessed March 8, 2021.
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