Diseño de puestos y funciones

Lymphocyte homing to LNs and other lymphoid tissues is required for peripheral tolerization to alloantigen. CCR7 essentially guides T cells to home into LNs and CCR7 deficiency severely impairs the migration of lymphocytes to LNs. Manoeuvres that interfere with signal 1 and signal 2 of T cell activation via blockade of CD40-CD40L pathway can result in alloantigen-specific tolerance. However, using a murine heterotopic heart transplantation model, I observed that they are not applicable in vascularized organ transplantation under CCR7 deficiency.

I observed a modest prolongation of the full MHC mismatched cardiac allograft survival in CCR7-/- recipients compared with WT recipients under non- immunosuppressive therapy. Furthermore, present results also demonstrate that CCR7-/- T cells cannot reject allografts efficiently in CCR7-/- T cell immune reconstituted hosts. However, alloantigen-specific tolerance cannot be induced in CCR7-/- hosts under tolerance inducing treatment with donor specific transfusion plus CD40-CD40L blockade. Moreover, no beneficial effect of a short-course FTY720 administration was found on the full MHC mismatched cardiac survival in CCR7-/- recipients while combined treatment with CD40-CD40L blockade plus donor specific transfusion. Together, my data suggested that CCR7 plays a key role in transplant immunity.

As T cells are vital in orchestrating the immune response to alloantigens, I focused on T cell subsets in my study. I observed that a significantly increased number of effector/memory T cells infiltrated into allografts and accumulated in pLNs of CCR7-/- hosts under the treatment of donor specific transfusion plus CD40-CD40L blockade. Present data demonstrate that intragraft infiltrating CCR7-/- Tregs are inefficient in controlling graft rejection. Present results also show a CCR7-dependent homing of Tregs to peripheral LNs. These results are in accordance with a role of these cells in inducing tolerance to vascularized organ transplantation.

Cumulatively, CCR7 mediated lymphocyte trafficking is essentially required in transplant tolerance induction.

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7. Appendix

Declaration

Herewith, I confirm that I have written the present Dr. med thesis myself and independently, and that I have not submitted it to any other university worldwide.

Hannover, 18th of June 2008

Xiaosun Liu

Curriculum Vitae

Name: Xiaosun Liu

Presentation

13th ESOT (European Society for Organ Transplantation) Congress Prague, 2007 CCR7 Deficiency Prevents Tolerance Induction in a Murine Heart

Transplantation Model

Beckmann JH, Liu XS, Wemhoff D, Römermann D, Förster R, Hoffmann MW and Klempnauer J

August, 1975 Born in Jiujiang, China

1981-1986 Primary school in Jiujiang, China 1986-1992 Middle school in Jiujiang, China 1992-1997

1997-2001

Medical student in Medical School, Nanchang University, China (conferred the Bachelor’s degree of Medical Science)

Resident in the department of abdominal surgery, Jiangshan Hospital, Jiangshan City, China.

2001-2004 Medical student in Medical School, Zhejiang University, China. (conferred the Master’s degree of Medicine)

2004- 2006 Resident in the department of abdominal surgery, First Affiliated Hospital , Zhejiang University, China

July, 2006 Promotion to Attending surgeon in the department of abdominal surgery, First Affiliated Hospital, Zhejiang University, China

October, 2006-

Institute of Immunology, Hannover Medical School, Hannover, Germany

Acknowledgements

First, I’d like to express my immense gratitude to Prof. Dr. Reinhold Förster for providing me the opportunity to make research in his group. These unforgettable days in Hannover will become the most precious story in my life, owing to Prof. Förster’s kindness and generosity.

I also wish to give special acknowledgements to:

Dr. Jan Beckmann, for his profound help in the research.

Prof. Dr. Matthias Hoffmann, the director of General and Visceral Surgery Department, Raphaelskinik Münster, for his profound help in the research.

Prof. Dr. Klempnauer, the director of Visceral and Transplantation Surgery Department, and Prof. Dr. Schwinzer, the leader of Transplantation Labor, for affording the necessity for my studies.

Ph. D student Jessica Kocks, for her crucial help in my experiment. Miss Dorothee Römermanm, Miss Katharine Hoffmann for their excellent technical assistance in the lab.

Prof. Dr. Shusen Zheng, the director of the Surgery Department of the 1st

Affiliated Hospital of Zhejiang University, for the agreement of my Hannover trip. Prof. Dr. Jiren Yu, the director of the department of gastroenterological surgery in the 1st Affiliated Hospital, Zhejiang University, for his great contributions to my career.

Dr. Song Rong, Dr. Sheng Yan, Dr. Jiong Tian, Dr. Penghong Song and Miss Meilian Yao for their help in my study abroad.

Many thanks to all the people who have supported me through the time of My MD work.

Finally, I am so grateful to my wife Minjie Mao, my son Yutong Liu and my parents for their love, support and understanding in my life. I owe them that much, beyond words.

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