αβ T Cell Receptor Transfer to γδ T Cells Generates Functional Effector Cells without Mixed TCR Dimers In Vivo

作者: Lars T. van der Veken , Miriam Coccoris , Erwin Swart , J. H. Frederik Falkenburg , Ton N. Schumacher

DOI: 10.4049/JIMMUNOL.182.1.164

关键词:

摘要: The successful application of T cell-based immunotherapeutic applications depends on the availability large numbers cells with desired Ag specificity and phenotypic characteristics. Engineering TCR-transferred lymphocytes is an attractive strategy to obtain sufficient choice. However, introduction additional TCR chains into leads generation unknown specificity, due formation mixed dimers between endogenous introduced chains. such potentially autoaggressive may be prevented by using gammadelta as recipient cells, but in vivo activity TCR-engineered has not been established. In present study, we have investigated functionality TCR-transduced particular their specific proliferative capacity, reactivity, persistence, capacity mount recall responses. results demonstrate that alphabeta engineering forms a feasible generate Ag-specific effector do express dimers. view increasing concerns potential autoimmune consequences dimer formation, testing engineered clinical trials seems warranted.

参考文章(51)
HJ Kolb, J Mittermuller, C Clemm, E Holler, G Ledderose, G Brehm, M Heim, W Wilmanns, Donor Leukocyte Transfusions for Treatment of Recurrent Chronic Myelogenous Leukemia in Marrow Transplant Patients Blood. ,vol. 76, pp. 2462- 2465 ,(1990) , 10.1182/BLOOD.V76.12.2462.2462
Shigeyoshi Itohara, Andrew G. Farr, Juan J. Lafaille, Marc Bonneville, Yohtaroh Takagaki, Werner Haas, Susumu Tonegawa, Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia Nature. ,vol. 343, pp. 754- 757 ,(1990) , 10.1038/343754A0
Helmut W. H. G. Kessels, Monika C. Wolkers, Marly D. van den Boom, Martin A. van den Valk, Ton N. M. Schumacher, Immunotherapy through TCR gene transfer. Nature Immunology. ,vol. 2, pp. 957- 961 ,(2001) , 10.1038/NI1001-957
Thomas Goodman, Leo Lefrançois, Expression of the γ-δ T-cell receptor on intestinal CD8+ intraepithelial lymphocytes Nature. ,vol. 333, pp. 855- 858 ,(1988) , 10.1038/333855A0
Miriam Coccoris, Erwin Swart, Moniek A. de Witte, Jeroen W. J. van Heijst, John B. A. G. Haanen, Koen Schepers, Ton N. M. Schumacher, Long-Term Functionality of TCR-Transduced T Cells In Vivo Journal of Immunology. ,vol. 180, pp. 6536- 6543 ,(2008) , 10.4049/JIMMUNOL.180.10.6536
Thomas Stanislawski, Ralf-Holger Voss, Carina Lotz, Elena Sadovnikova, Ralph A. Willemsen, Jürgen Kuball, Thomas Ruppert, Reinder L. H. Bolhuis, Cornelius J. Melief, Christoph Huber, Hans J. Stauss, Matthias Theobald, Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nature Immunology. ,vol. 2, pp. 962- 970 ,(2001) , 10.1038/NI1001-962
Yun Shen, Dejiang Zhou, Liyou Qiu, Xioamin Lai, Meredith Simon, Ling Shen, Zhongchen Kou, Qifan Wang, Liming Jiang, Jim Estep, Robert Hunt, Michelle Clagett, Prabhat K Sehgal, Yunyaun Li, Xuejun Zeng, Craig T Morita, Michael B Brenner, Norman L Letvin, Zheng W Chen, Adaptive Immune Response of Vγ2Vδ2+ T Cells During Mycobacterial Infections Science. ,vol. 295, pp. 2255- 2258 ,(2002) , 10.1126/SCIENCE.1068819
Jessica Jones-Carson, Andres Vazquez-Torres, Henri C. van der Heyde, Thomas Warner, R. Doug Wagner, Edward Balish, Gamma delta T cell-induced nitric oxide production enhances resistance to mucosal candidiasis. Nature Medicine. ,vol. 1, pp. 552- 557 ,(1995) , 10.1038/NM0695-552
David J. Topham, Maria R. Castrucci, F. Suzette Wingo, Gabrielle T. Belz, Peter C. Doherty, The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia Journal of Immunology. ,vol. 167, pp. 6983- 6990 ,(2001) , 10.4049/JIMMUNOL.167.12.6983
Helmut W. H. G. Kessels, Koen Schepers, Marly D. van den Boom, David J. Topham, Ton N. M. Schumacher, Generation of T cell help through a MHC class I-restricted TCR. Journal of Immunology. ,vol. 177, pp. 976- 982 ,(2006) , 10.4049/JIMMUNOL.177.2.976