Inhibition of T cell homing by down-regulation of CD62L and the induction of a Th-2 response as a method to prevent acute allograft rejection in mice

Stremmel, Christian; Sienel, Wulf; Eggeling, Stephan; Passlick, Bernward; Slavin, Anthony
August 2006
European Journal of Cardio-Thoracic Surgery;Aug2006, Vol. 30 Issue 2, p362
Academic Journal
Abstract: Objective: For a successful immune response, migration of lymphocytes to lymphoid organs and other tissues is a key step, as the initial recognition of foreign antigens and activation of lymphocytes takes place in these organs. CD62L is a homing receptor that mediates entry of naïve T cells to peripheral lymph nodes. Maybe the preventing of T cell homing will change the immune response against allogeneic tissue and suppress rejection. Methods: We treated different mouse strains with pertussis toxin to manipulate T cell homing and measured the rejection of allografts in terms of allogeneic tumor cells. We transferred pertussis toxin treated or nontreated transgenic T cells into BALB/c wild type mice. The transgenic T cells could be followed ex vivo by specific antibodies. Cytokine production from purified (1×105/ml) T cells after different stimulations in vitro and expression of surface markers on T cells following pertussis toxin treatment by FACS analysis were performed. Results: Pertussis toxin-treated C57BL/6 mice with the MHC class I molecule H-2Kb could not reject allogeneic tumor cells R1.1, which expressed the MHC class I molecule H-2Kk and were killed by these cells. This allograft survival could be demonstrated for various allogeneic cells in different mouse strains with different MHC class I expression and emphasizes the general mechanism in these studies. In vivo CD62L expression on T cells was down-regulated by pertussis toxin in normal mice and transgenic mice that produce only one specific T cell, and after the pertussis toxin treatment the mice showed 4–5 times larger spleens compared to untreated mice. In transfer experiments, we demonstrated that CD62L low transgenic T cells could not home to lymph nodes. Furthermore, spleen cells from pertussis toxin-treated mice produced high amounts of the Th-2 cytokine interleukin 4 after stimulation in primary culture. Conclusions: Our data suggest that the inhibition of T cell homing changes the immune response. Prevention of homing of T cells in combination with the induction of a Th-2 response is a mechanism to prevent specific acute rejection of allogeneic tissue.


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