Transient Lymphopenia Breaks Costimulatory Blockade-Based Transplant Tolerance and Initiates Allograft Rejection
1Urology, Tokyo Women's Medical Univ, Tokyo, Japan
2Immunology, Science University of Tokyo, Chiba, Japan
3Immunology, Cleveland Clinic, Cleveland, OH.
Meeting: 2015 American Transplant Congress
Abstract number: D5
Keywords: FACS analysis, Lymphocyte activation, Mice, T cell reactivity
Session Information
Session Name: Poster Session D: Costimulation and Signaling in Lymphocytes
Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
【Background and Objective】: Lymphopenia is induced by lymphoablative therapies and chronic viral infections. Lymphopenia is observed in some pathological and physiological processes, including chronic viral infection, emigration of newly selected T cells from the thymus into the periphery prior to complete development of the repertoire and the sequential administration of calcineurin inhibitors. We assessed the impact of lymphopenia on cardiac allograft survival in recipients conditioned with peritransplant costimulatory blockade (CB) to promote long-term graft acceptance.
【Materials and Methods】
Vascularized heterotopic cervical heart transplantation from BALB/c donors to recipient B6 mice was performed using a nonsuture cuff technique. After heart grafts were stably accepted through CB, lymphopenia was induced on day 60 posttransplant by 6.5 Gy irradiation or by administration of anti-CD4 plus anti- CD8 mAb.
【Results】
Long-term surviving allografts were gradually rejected after lymphodepletion (MST . 74 ±5 days postirradiation). Histological analyses indicated signs of severe rejection in allografts following lymphodepletion, including mononuclear cell infiltration and obliterative vasculopathy. Lymphodepletion of CB conditioned recipients induced increases in CD44high effector/memory T cells in lymphatic organs and strong recovery of donor-reactive T cell responses, indicating lymphopenia-induced proliferation (LIP) and donor alloimmune responses occurring in the host. T regulatory (CD4+ Foxp3+ ) cell and B cell numbers as well as donor-specific antibody titers also increased during allograft rejection in CB conditioned recipients given lymphodepletion.
【Conclusion】
These observations suggest that allograft rejection following partial lymphocyte depletion is mediated by LIP of donor-reactive memory T cells. As lymphopenia may cause unexpected rejection of stable allografts, adequate strategies must be developed to control T cell proliferation and differentiation during lymphopenia.
To cite this abstract in AMA style:
Iida S, Suzuki T, Tanabe K, Valujskikh A, Fairchild R, Abe R. Transient Lymphopenia Breaks Costimulatory Blockade-Based Transplant Tolerance and Initiates Allograft Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/transient-lymphopenia-breaks-costimulatory-blockade-based-transplant-tolerance-and-initiates-allograft-rejection/. Accessed May 12, 2025.« Back to 2015 American Transplant Congress