Effect of Infection and Acute Cellular Rejection on T Cell Populations in Post-Lung Transplant Biopsy Specimens
K Suzue, SM Bhorade, M Tretiakova, YX Fu, AN Husain. Mount Sinai Hospital, Chicago, IL; University of Chicago, Chicago, IL
Background: Episodes of infection and acute rejection are risk factors for subsequent chronic lung transplant rejection. A better understanding of the inflammatory milieu within lung allografts is crucial for improving immunosuppressive regimens and survival in lung transplant (LTx) recipients. Recent studies have suggested a role for CD4+ T cells expressing FoxP3 in inhibiting the CD8+ anti-cellular T cell response and inducing immunotolerance. This study assessed the populations of T cells present in LTx biopsy specimens.
Design: We evaluated 21 LTx transbronchial biopsy specimens, which were divided as: Group 1 (n=5) positive for acute cellular rejection (A1BX, A1BX, A2B0, A2B0, A2B2); Group 2 (n=8) positive for viral infection (CMV, influenza, RSV) and Group 3 (n=8) negative for infection and acute cellular rejection. We confirmed these diagnoses on H&E sections and by clinical history. We then immunostained for CD3, CD4, CD8, CD20 and FoxP3 and examined the interstitial and perivascular infiltrates. (Scored: '0' for no positive cells; '1' for 1 cell/40X; '2' for 2-8 cells/40X, '3' for >8 positive cells at 40X and '4' for diffusely positive cells at 4X.).
Results: All 21 cases contained a higher proportion of CD8+ T cells in the interstitium, relative to CD4+ T cells (avg CD4:CD8 of 1:6). In group 3 (no rejection or infection), further analysis of T cells was not done due to the minimal inflammatory cell infiltrate. In group 1 (acute cellular rejection group), 1-10% (mean 8%) of interstitial T cells were FoxP3+, and the perivascular FoxP3+ T cell infiltrate was 10%-20% FoxP3+ T cells. In contrast, in group 2 (viral infection group), rare to absent (0-4%; mean 1%) (p=0.002) interstitial FoxP3+ T cells were seen despite a 3+ to 4+ level of CD3+ T cell infiltration.
Conclusions: This preliminary study illustrates the difference in T cell populations in LTx allografts in patients with acute cellular rejection vs. infection. Specifically, viral infections led to lower numbers of FoxP3+ T cells and may be a mechanism by which viral infections contribute to chronic lung allograft rejection. Evaluation of regulatory T cells as well as other immunologic mediators and markers will contribute to our understanding of lung transplant immunopathology. Indeed, manipulation of specific T cell subsets may be an effective strategy for inducing lung transplant tolerance.
Monday, March 9, 2009 1:00 PM
Poster Session II # 236, Monday Afternoon