EuroMAbNet: European Monoclonal Antibodies Network

Members

José I. Rodríguez Barbosa

Name of the laboratory

Members of the laboratory

Unit Coordinator. Professor of Immunology

José I. Rodríguez Barbosa ignacio.barbosa@unileon.es

Miguel Servet Investigator. Associate Professor of Immunology

Maria Luisa del Río González mlriogon@saludcastillayleon.es

Technician

Gonzalo Rando Olmo

PhD students

Irene del Vigo Soto

Laboratory activity

Rejection of allogeneic tissues and organs is an immunological phenomenon mediated by T cells and antibodies. The rejection of transplanted vascularized solid organs across MHC histocompatibility barriers requires continuous and prolonged use of immunosuppressive drugs, which are responsible for long-term serious side effects. Therefore, those therapeutic interventions or strategies to reduce or ideally eliminate immunosuppressive medication that allow the induction of immunological tolerance would achieve long-term graft survival and the improvement in the quality of life of transplanted patients.

The final goal of our laboratory is the identification and validation of molecular targets essential for the exchange of information between dendritic cells / T cells and T/ B cells for the modulation of the allogeneic humoral and cellular mediated immune responses.

1) Prevention of allograft rejection by interfering with the collaboration of dendritic cells / B / T cells through blockade of costimulatory signals or the enhancement of negative signaling to T cells (coinhibitory signals).

2) Prevention of rejection by the selective elimination of T cells responsive to alloantigen, targeting molecules that are restrictively expressed upon T cell activation.

To address these objectives, we applied biochemical techniques, molecular biology, cellular and animal models of skin and bone marrow transplantation. We amplify genes of interest involved in particular pathways of cell interaction, which are then cloned and expressed as membrane bound proteins and soluble proteins (extracellular regions). Soluble recombinant proteins are purified from culture supernatant of transfected cells and use as antigens for the generation of antibodies with different effector functions (agonist, antagonist, depleting, non-depleting). Finally, these antibodies and recombinant proteins are used as therapeutic tools in vitro and in vivo to test their efficacy in preventing allogeneic immune responses across different histocompatibility barriers to dissect the mechanisms involved in graft rejection and tolerance.

The ultimate goal of the lab is to prove that the experimental strategies developed in the course of our studies are able to prevent rejection in in vivo animal models of skin and bone marrow transplantation across different MHC histocompatibility barriers , where the rejection response is mediated by CD4 and CD8 T lymphocytes and anti-donor specific antibodies.

Publications (2020-present)

• CD160 serves as a negative regulator of NKT cells in acute hepatic injury. Kim TJ, Park G, Kim J, Lim SA, Kim J, Im K, Shin MH, Fu YX, Del Rio ML, Rodriguez-Barbosa JI, Yee C, Suh KS, Kim SJ, Ha SJ, Lee KM. Nat Commun. 2019 Jul 22;10(1):3258. doi: 10.1038/s41467-019-10320-y. PMID:31332204
• HVEM, a cosignaling molecular switch, and its interactions with BTLA, CD160 and LIGHT. Rodriguez-Barbosa JI, Schneider P, Weigert A, Lee KM, Kim TJ, Perez-Simon JA, Del Rio ML. Cell Mol Immunol. 2019 Jul;16(7):679-682. doi: 10.1038/s41423-019-0241-1. Epub 2019 Jun 3. No abstract available. PMID:31160757
• Divya Sekar, Luisa Govene, María Luisa del Río, Evelyn Sirait-Fischer, Annika Fink, Bernhard Brüne, Jose Ignacio Rodriguez-Barbosa, Andreas Weigert. Downregulation of BTLA activates NKT cells and promotes tumor immune control in a mouse model of mammary carcinoma. International Journal of Molecular Sciences (Manuscript ID: ijms-275430, accepted). 2018.
• Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation. Rodriguez-Barbosa JI, Ferreras MC, Buhler L, Jones ND, Schneider P, Perez-Simon JA, Del Rio ML. MAbs. 2018 Oct;10(7):1030-1044. doi: 10.1080/19420862.2018.1502127. Epub 2018 Sep 5. PMID: 30036156
• Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma. Sekar D, Govene L, Del Río ML, Sirait-Fischer E, Fink AF, Brüne B, Rodriguez-Barbosa JI, Weigert A. Int J Mol Sci. 2018 Mar 7;19(3). pii: E752. doi: 10.3390/ijms19030752
• Modulation of cytotoxic responses by targeting CD160 prolongs skin graft survival across major histocompatibility class I barrier. Del Rio ML, Bravo Moral AM, Fernandez-Renedo C, Buhler L, Perez-Simon JA, Chaloin O, Alvarez Nogal R, Fernandez-Caso M, Rodriguez-Barbosa JI. Transl Res. 2017 Mar;181:83-95.e3. doi: 10.1016/j.trsl.2016.09.004. Epub 2016 Sep 15. PMID: 27702550
• T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway. Rodriguez-Barbosa JI, Fernandez-Renedo C, Moral AMB, Bühler L, Del Rio ML. Cell Mol Immunol. 2017 Jun;14(6):497-510. doi: 10.1038/cmi.2015.101. Epub 2016 Feb 29. PMID: 26924526. Free PMC Article
• G. Roncador, G., P. Engel, L. Maestre, A. P. Anderson, J. L. Cordell, M. S. Cragg, V. C. Serbec, M. Jones, V. J. Lisnic, L. Kremer, D. Li, F. Koch-Nolte, N. Pascual, J. I. Rodriguez-Barbosa, R. Torensma, H. Turley, K. Pulford, and A. H. Banham. 2016. The European antibody network's practical guide to finding and validating suitable antibodies for research. mAbs 8(1): 27-36.
• M.L. del Rio, C. Fernandez-Renedo, O. Chaloin, S. Scheu, K. Pfeffer, Y. Shintani, J. A. Perez-Simon, P. Schneider, and J.I. Rodriguez-Barbosa. 2016. Immunotherapeutic targeting of LIGHT/LTbetaR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells. mAbs 11: 1-13.
• H. Arefanian, E. B. Tredget, D. C. Mok, Q. Ramji, S. Rafati, J.I. Rodriguez-Barbosa, G. S. Korbutt, R. V. Rajotte, R. G. Gill, and G. R. Rayat. 2016. Porcine Islet-Specific Tolerance Induced by the Combination of Anti-LFA-1 and Anti-CD154 mAbs Is Dependent on PD-1. Cell transplantation 25: 327-342.
• Sanchez-Abarca, L. I., E. Hernandez-Galilea, R. Lorenzo, C. Herrero, A. Velasco, S. Carrancio, T. Caballero-Velazquez, J.I. Rodriguez-Barbosa, M. Parrilla, C. Del Canizo, J. San Miguel, J. Aijon, and J. A. Perez-Simon. 2015. Human Bone Marrow Stromal Cells Differentiate Into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice. Cell transplantation 24: 2423-2433.
• M.L. del Rio, C. Fernandez-Renedo, S. Scheu, K. Pfeffer, Y. Shintani, M. Kronenberg, O. Chaloin, P. Schneider, and J.I. Rodriguez-Barbosa. 2014. Therapeutic blockade of LIGHT interaction with herpesvirus entry mediator and lymphotoxin beta receptor attenuates in vivo cytotoxic allogeneic responses. Transplantation 98: 1165-1174.
• S.J. Allen,, A. Rhode-Kurnow, K. R. Mott, X. Jiang, D. Carpenter, J.I. Rodriguez-Barbosa, C. Jones, S. L. Wechsler, C. F. Ware, and H. Ghiasi. 2014. Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. Journal of virology 88: 1961-1971.
• Maria-Luisa del Rio, Jörg D. Seebach, and Jose-Ignacio Rodriguez-Barbosa. Negative signaling pathways for the control of xenogeneic immune responses. Xenotransplantation. 2013 Nov-Dec;20 (6) :397-406. 2013.
• Maria-Luisa del Rio, Pascal Schneider, Carlos Fernández-Renedo, Jose Antonio Pérez Simón, and Jose-Ignacio Rodriguez-Barbosa. LIGHT/HVEM/LTbR interaction as a target for the modulation of the allogeneic immune response in transplantation. American Journal of Transplantation. 13 (3) :541-51, 2013.
• Maria-Luisa del Rio, Nick D. Jones, Leo Buhler, Paula Norris, Yasushi Shintani, Carl F. Ware and Jose-Ignacio Rodriguez-Barbosa. Selective blockade of HVEM-BTLA pathway ameliorates acute graft-versus-host reaction. Journal of Immunology. 188 (10): 4885-96, 2012.
• Isabel Moscoso, Jose-Ignacio Rodriguez-Barbosa, Javier Barallobre-Barreiro, Patricia Anon and Nieves Domenech. Immortalization of bone marrow-derived porcine mesenchymal stem cells and their differentiation into cells expressing cardiac phenotypic markers. Journal of Tissue Engineering and Regenerative Medicine. 2012. 6(8): 655-65, 2012.
• Maria-Luisa del Rio, Josef Kurtz, Claudia Perez-Martinez, Arnab Ghosh, José Antonio Pérez-Simón and Jose-Ignacio Rodriguez-Barbosa. Targeting BTLA protects against the acute phase of GvHR in a murine model of alloreactivity by inhibiting donor anti-host cytotoxicity. Transplantation. Nov 27;92 (10):1085-1093. 2011.
• Maria-Luisa del Rio, Javier Cote-Sierra, Jose-Ignacio Rodriguez-Barbosa. Flt3 ligand-mobilized dendritic cells loaded with H-2Kbm1 apoptotic cells do not induce cross-tolerance to allogeneic CD8+ T cells across a class I MHC mismatched barrier. Transplant International. 24 (5): 501-13, 2011.
• Maria-Luisa del Rio, Gunter Bernhardt, Jose-Ignacio Rodríguez-Barbosa and Reinhold Forster. Development and functional specialization of CD103+ dendritic cells. Immunological Reviews. 234 (1): 268-281, 2010.
• Maria-Luisa del Rio, Jonathan Kaye, and Jose-Ignacio Rodriguez-Barbosa. In vivo antibody-mediated down-modulation of BTLA on lymphoid and myeloid cells of mice expressing either C57BL/6 or BALB/c BTLA allelic variants. Immunobiology. 215 (7): 570-8, 2010.
• M.L. del Rio, C. Gibbons, G. Rayat, L. Buhler and Jose-Ignacio Rodriguez-Barbosa. HVEM/BTLA/CD160/LIGHT co-signaling pathway as target for immune regulation. Journal of Leukocyte Biology. 87 (2): 223-235, 2010.
• Jiong Tian, Jose-Ignacio Rodriguez-Barbosa; Oliver Pabst; Dorothee Roemermann; Reinhold Foerster; Jan Beckmann; Matthias W Hoffmann. ADAP deficiency combined with costimulation blockade synergistically protect intestinal allografts. Transplant International. 23(1): 71-9, 2010.
• Maria-Luisa del Río, José-Ignacio Rodríguez-Barbosa, Jasmin Bölter, Matthias Ballmaier, Oliver Dittrich-Breiholz, Michael Kracht, Steffen Jung, and Reinhold Förster. CX3CR1+c-kit+ bone marrow cells give rise to CD103+ and CD103- dendritic cells with distinct functional properties. Journal of Immunology. 181 (9):6178-6188, 2008.
• M.L.del Rio, L. Buhler, C. Gibbsons, J. Tian and J.I. Rodriguez-Barbosa. PD-1/PD-L1 and PD-1/PD-L2 pathways and other co-inhibitory molecules signaling pathways in transplantation. Transplant International. 21 (11):1015-1028, 2008.