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LACK OF CHRONIC LUNG ALLOGRAFT REJECTION IS ASSOCIATED WITH EXPANSION OF REGULATORY CD4+CD25+ AND CD4+CD28- T CELLS AND A PREDOMINANT TH2 ALLOREACTIVITY.
Andres Jaramillo, Kishore Narayanan, Lacey G. Campbell, Nancy S. Steward, Elbert P. Trulock, G. Alexander Patterson and T. Mohanakumar. St. Louis MO, Washington University, Surgery and St. Louis MO, Washington University, Medicine.

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Purpose: There is a correlation between a lack of T cell alloreactivity and a lack of chronic rejection (bronchiolitis obliterans syndrome [BOS]) after lung transplantation (LT). However, HLA class I and II mismatches are comparable between BOS+ and BOS- LT patients. Thus, the aim of this study was to determine if the lack of T cell alloreactivity in BOS- patients is due to the activation of putative regulatory T cells (CD4+CD25+, CD4+CD28-, and CD8+CD28-).
Methods: Fourteen BOS+ patients, 13 BOS- patients, and 10 healthy controls were included in this study. The regulatory T cells were analyzed by flow cytometry for the expression of the CD45RO memory T cell marker. In addition, the frequencies of alloreactive CD4+ Th1 and Th2 cells were determined by IFN-γ and IL-5 ELISPOT assays, respectively.
Results: There was a significant expansion of CD4+CD25+, CD4+CD28-, and CD8+CD28- T cells in LT patients as compared to healthy controls (p<0.01) indicating that all these T cell subpopulations are expanded after LT. There were no differences between the levels of the CD4+CD25+, CD4+CD28-, and CD8+CD28- T cells between BOS+ and BOS- patients. However, there was a significant increase of memory (CD45RO+) CD4+CD25+ and CD4+CD28- T cells (p<0.01) in the BOS- patients as compared to the BOS+ patients. Moreover, BOS- patients had a significantly higher frequency of alloreactive CD4+ Th2 cells as compared to BOS- patients (p<0.01).
Conclusion: Activation of regulatory CD4+CD25+ and CD4+CD28- T cells is associated with Th2 alloreactivity and lack of BOS development after LT.