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

• Published in: European journal of cardio-thoracic surgery 2006-08, Vol.30 (2), p.362-369
• Main Authors: Stremmel, Christian, Sienel, Wulf, Eggeling, Stephan, Passlick, Bernward, Slavin, Anthony
• Format: Article
• Language: English
• Subjects: Acute Disease; Adoptive Transfer; Allograft rejection; Animals; CD62L; Cell Movement - immunology; Cell Proliferation; Cells, Cultured; Cytokines - biosynthesis; Down-Regulation - immunology; Female; Graft Rejection - immunology; Graft Rejection - prevention & control; Homing; Immune Tolerance; L-Selectin - immunology; L-Selectin - metabolism; Lymphocyte Activation - immunology; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Pertussis Toxin - immunology; Th2 Cells - immunology; Transplantation; Tumor Cells, Cultured
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1016/j.ejcts.2006.04.014

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.