ACTIVATION AND ROLE OF T REGULATORY CELLS

I. Klein¹, N.K. Polakos², D.J. Topham³, N.I. Crispe^4
1Surgery, University of California San Francisco (UCSF), San Francisco/CA/UNITED STATES OF AMERICA, ²Anatomy, University of California, San Francisco, San Francisco/CA/UNITED STATES OF AMERICA, ³Microbiology And Immunology, David H. Smith CVBI, Rochester/NY/UNITED STATES OF AMERICA, ⁴, 4Seattle Biomedical Research Institute, Seattle/UNITED STATES OF AMERICA

Body: Introduction: During liver transplantation, immune competent donor cells are transferred to the recipient, which may alter the recipient’s immune-repertoire. In this study, a standardized model was used to evaluate the role of donor-derived influenza-specific CD8 memory T cells during re-infection in the recipient. Methods: Liver grafts from previously influenza-immunized donor mice were transplanted into naive recipients and the recipient's immune response was evaluated upon re-infection: B6.CD45.2 donor mice were infected with pulmonary influenza (A/HKx31; H3N2) and their livers were transplanted into naive recipients (B6.CD45.1) 28days after infection. The transplant recipients were re-infected with pulmonary influenza (A/PR/8/34) four weeks following orthotopic liver transplantation. Proliferation of virus-specific cytotoxic T cells was assessed by flow cytometric tetramer staining. The functional capacity of the virus-specific T cells was evaluated by cytokine secretion and in-vivo cytotoxicity. Results: Four weeks after liver transplantation about 3000 donor-specific memory T cells were detectable in the recipients' liver and lymphatic organs. Re-infection with influenza resulted in massive proliferation of the donor-derived, virus-specific CD8 T cells to up to 85% of the total virus-specific immune response in the recipient. The dominance of the donor-derived memory T cell population suppressed the regular extent of the recipient-specific immune response seen in transplant recipients of non-immunized liver grafts. In functional analysis, a rapid secretion of type-1 cytokines and cytotoxic effector function was seen in transplant recipients of immunized liver grafts. Conclusion: Transferred memory T cells from donor livers can participate in immune responses in the transplant recipient and even dominate them. This may result in adoptive immunization of transplant recipients against virus infections and other pathogens as well as transfer of unwanted allergies or autoimmune diseases. In contrast to common clinical practice, more attention should be paid to the immunological condition of the organ donor. In living donor liver transplantation, immunization of organ donors might result in reduced re-infection rates in the organ recipient.

Disclosure: All authors have declared no conflicts of interest.