Journal of Cell Science & Therapy
Open Access

Targeting high affi nity LFA-1 to prevent GVHD and preserve GVL

International Conference & Exhibition on Cell Science & Stem Cell Research

29 Nov - 1 Dec 2011 Philadelphia Airport Marriott, USA

Qing Ma

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

Allogeneic bone marrow transplantation (alloBMT) is an eff ective therapy for hematological malignancies. But the limiting factor is graft -versus-host disease (GVHD), and the same T cell-mediated alloimmune responses are strongly associated with the benefi cial graft - versus leukemia (GVL) eff ect. Th erefore, alloBMT has been exploited as a platform to deliver immunotherapy for leukemia and other malignant di seases. LFA-1 regulates T cell activation via immunological synapse and is constitutively expressed in the low affi nity state. LFA-1 changes to the high affi nity state upon activation which is an important mechanism for regulation. We found that high affi nity LFA-1 regulates T cell activation and proliferation. Th e activation of LFA-1 directly enhances TCR signal pathway, thus decreasing T cell activation threshold by promoting IL-2 production and proliferation. Although blocking high affi nity LFA-1 can inhibit the proliferation of human cytotoxic T lymphocytes (CTL) upon TCR and antigen-specifi c stimulation, their antigen-specifi c cytotoxic function against target cells remains intact. T cell proliferation requires mature synapse formation aft er prolonged stimulation and high affi nity LFA-1 generates an additional signal to enhan ce T cell activation. In contrast, the CD8+ CTL secretory synapse for targeted delivery and cytolytic response is transient and does not require the high affi nity LFA-1. Previous studies report that eff ector T cells are responsible for GVL while the proliferation and diff erentiation of na�ve T cells contribute to GVHD. Th e high affi nity LFA-1 promotes na�ve T cell activation and mediates GVHD. Meanwhile low affi nity LFA-1 is suffi cient for the secretory synapse formation and cytolitic function to mediate GVL. Th e diff erential immunomodulatory eff ects of LFA-1 on the T cell proliferation versus cytoxicity provide a mechanistic explanation for GVHD and GVL, and targeting high affi nity LFA-1 can prevent GVHD while preserve GVL

Biography :

Qing Ma has completed her Ph.D. from Thomas Jefferson University and postdoctoral studies from Harvard medical School. She is an associate professor in the department of stem cell transplantation and cellular therapy at University of Texas M.D. Anderson Cancer Center