Research Projects

T lymphocytes, which are a subtype of white blood cell, play a central role in cell-mediated immunity. They are distinguished from other lymphocytes, such as B cells and natural killer (NK) cells, by the expression of a T cell receptor (TCR) on the cell surface. Team 1 has been working for decades on the immunobiology of human T lymphocytes that express either αβ or γδ TCR. The team was made of three subgroups which addressed complementary issues dealing with the immunobiology of human T lymphocytes and their immunotherapeutic use against infections and cancers.

In line with recent observations made by the team and its unique expertise that was recently strengthened by additional members and clinicians, our joint objectives are to pursue from a fundamental standpoint the analysis of the specificity and function(s) of human T lymphocyte subsets (e.g., αβ/γδ T and NK cells) and the impact of selected interleukins, such as IL-15, in physiopathological contexts. From both preclinical & clinical standpoints, the research work focuses on:
(i) the ways to optimize immunotherapies targeting human lymphoid subsets (e.g., development of orthotopic in vivo models);
(ii) the analysis of alloreactive T lymphocyte responses elicited along allograft transplantation, in relation with both clinical status and allograft outcome in patients;
(iii) the design of novel in vitro tools for medium-throughput screening approaches of lymphoid cell-mediated reactivities induced by therapeutic antibodies;
(iv) the biology of IL-15 and its therapeutical applications.

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Staff

E. Scotet, DR INSERM
H. Vié, DR INSERM
E. Mortier, CR CNRS
Y. Jacques, DR CNRS éméritat
R. Breathnach, PU
X. Saulquin, PU
L. Gautreau, MCU
F. Konczak-Del Gatto, MCU
C. Retière, CR EFS
K. Gagne, CR EFS
P. Chevallier, PU-PH
T. Guillaume, PH
M.C. Béné, PU-PH
M.C. Devilder, IR – CHU
B. Clémenceau, IR – CHU
C. Chauvin, Doctorant
J. Perroteau, Doctorant
N. Joalland, Doctorant
L. Boutin, Doctorant
M. Fernandes-Capitao, Doctorant
D. Meghnem, Doctorant
M. Frutoso, Doctorant
B. Maniangou, Doctorant
M.C. Gesnel, TR CHU
R. Vivien, IE INSERM
J. Ollier, IE CDD CHU
M. Moyon, TR CDD CHU
L. Lafrance, TN CDD INSERM
A. Quemener, IR Inserm
M. Maillasson, IE Inserm
I. Barbieux, AI Inserm
S. Morisseau IR CDD CHU
I. Leray,IE CDD Inserm,
K. Trillet, IE CDD Inserm
N. Legrand, TCH EFS
G. David-Bosquaux, TCH EFS
C. Willem, TCH EFS

Main Publications

Biology of IL-15
– Pacheco Y, Solé V, Billaud E, Allavena C, Plet A, Ferré V, Garrigue-Antar L, Raffi F, Jacques Y, McIlroy D. Despite an impaired response to IL-7, CD4+EM T cells from HIV-positive patients proliferate normally in response to IL-15 and its superagonist, RLI. AIDS. (2011).
– Vincent M, Bessard A, Cochonneau D, Teppaz G, Solé V, Maillasson M, Birklé S, Garrigue-Antar L, Quéméner A, Jacques Y. Tumor targeting of the IL-15 superagonist RLI by an anti-GD2 antibody strongly enhances its antitumor potency. Int J Cancer. (2013)
– Tamzalit F, Barbieux I, Plet A, Heim J, Nedellec S, Morisseau S, Jacques Y, Mortier E. IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells. Proc Natl Acad Sci U S A. (2014).

Optimization of Immunotherapies
– Clémenceau B, Vivien R, Debeaupuis E, Esbelin J, Biron C, Levy Y, Vié H. FcγRIIIa (CD16) induction on human T lymphocytes and CD16pos T-lymphocyte amplification. J Immunother. (2011)
– Santolaria T, Robard M, Léger A, Catros V, Bonneville M, Scotet E. Repeated systemic administrations of both aminobisphosphonates and human Vγ9Vδ2 T cells efficiently control tumor development in vivo. J Immunol. (2013)
– Vincent M, Teppaz G, Lajoie L, Solé V, Bessard A, Maillasson M, Loisel S, Béchard D, Clémenceau B, Thibault G, Garrigue-Antar L, Jacques Y, Quéméner A. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse. MAbs. (2014).
– Lajoie L, Congy-Jolivet N, Bolzec A, Gouilleux-Gruart V, Sicard E, Sung HC, Peiretti F, Moreau T, Vié H, Clémenceau B, Thibault G. ADAM17-mediated shedding of FcγRIIIA on human NK cells: identification of the cleavage site and relationship with activation. J Immunol. (2014)
– Gallot G, Vollant S, Saïagh S, Clémenceau B, Vivien R, Cerato E, Bignon JD, Ferrand C, Jaccard A, Vigouroux S, Choquet S, Dalle JH, Frachon I, Bruno B, Mothy M, Mechinaud F, Leblond V, Milpied N, Vié H. T-cell therapy using a bank of EBV-specific cytotoxic T cells: lessons from a phase I/II feasibility and safety study. J Immunother. (2014)
– Clémenceau B, Valsesia-Wittmann S, Jallas AC, Vivien R, Rousseau R, Marabelle A, Caux C, Vié H. In Vitro and In Vivo Comparison of Lymphocytes Transduced with a Human CD16 or with a Chimeric Antigen Receptor Reveals Potential Off-Target Interactions due to the IgG2 CH2-CH3 CAR-Spacer. J Immunol Res. (2015)
– Jarry U*, Chauvin C*, Joalland N, Léger A, Minault S, Robard M, Bonneville M, Oliver L, Vallette FM, Vié H, Pecqueur C, Scotet E.Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors. Oncoimmunology. (2016)
http://www.hal.inserm.fr/inserm-01342603

Analysis of NK cells and Killer-cell immunoglobulin-like receptors (KIR)
– Gagne K, Willem C, Legrand N, Djaoud Z, David G, Rettman P, Bressollette-Bodin C, Senitzer D, Esbelin J, Cesbron-Gautier A, Schneider T, Retière C. Both the nature of KIR3DL1 alleles and the KIR3DL1/S1 allele combination affect the KIR3DL1 NK-cell repertoire in the French population. Eur J Immunol. (2013)
– Djaoud Z, David G, Bressollette C, Willem C, Rettman P, Gagne K, Legrand N, Mehlal S, Cesbron A, Imbert-Marcille BM, Retière C. Amplified NKG2C+ NK cells in cytomegalovirus (CMV) infection preferentially express killer cell Ig-like receptor 2DL: functional impact in controlling CMV-infected dendritic cells. J Immunol. (2013)
– David G, Djaoud Z, Willem C, Legrand N, Rettman P, Gagne K, Cesbron A, Retière C. Large Spectrum of HLA-C Recognition by Killer Ig-like Receptor (KIR)2DL2 and KIR2DL3 and Restricted C1 Specificity of KIR2DS2: Dominant Impact of KIR2DL2/KIR2DS2 on KIR2D NK Cell Repertoire Formation. J Immunol. (2013)
– P. Rettman, N. Legrand, C. Willem, L. Lodé, P. Chevallier, A. Cesbron, D. Senitzer, C. Retière and K. Gagne.. 2015. Use of Killer cell Immunoglobulin-like Receptor (KIR) genes as new markers of haematopoietic chimerism after double-umbilical cord blood transplantation. Hematologica. (2015)
– Pauline Rettman, Catherine Willem, Gaëlle David, Raphaëlle Riou, Nolwenn Legrand, Julie Esbelin, Anne Cesbron, David Senitzer, Katia Gagne, Christelle Retière. New insights on the natural killer cell repertoire from a thorough analysis of cord blood cells. Journal of leukocyte biology. (2016)

Specificity and function of human unconventional Tγδ and NKT cells and conventional Tαβ  cells
– Legoux F, Debeaupuis E, Echasserieau K, De La Salle H, Saulquin X, Bonneville M.2010. Impact of TCR reactivity and HLA phenotype on naive CD8 T cell frequency in humans. J Immunol. (2010)
– Vié H, Gaschet J, Milpied N. Permissive, nonpermissive HLA-DPB1 epitope disparities and the specificity of T cells infiltrating the skin during acute graft-versus-host disease. Blood. (2011)
– Harly C, Guillaume Y, Nedellec S, Peigné CM, Mönkkönen H, Mönkkönen J, Li J, Kuball J, Adams EJ, Netzer S, Déchanet-Merville J, Léger A, Herrmann T, Breathnach R, Olive D, Bonneville M, Scotet E. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset. Blood. (2012)
– Legoux F, Gautreau L, Hesnard L, Leger A, Moyon M, Devilder MC, Bonneville M, Saulquin X. Characterization of the human CD4(+) T-cell repertoire specific for major histocompatibility class I-restricted antigens. Eur J Immunol. (2013)
– Hesnard L, Legoux F, Gautreau L, Moyon M, Baron O, Devilder MC, Bonneville M, Saulquin X. 2016. Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus. Eur J Immunol. (2016)
– Sandstrom A, Peigné CM, Léger A, Crooks JE, Konczak F, Gesnel MC, Breathnach R, Bonneville M, Scotet E*, Adams EJ*. The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vγ9Vδ2 T cells. Immunity. (2014)
– Peigné CM, Léger A, Gesnel MC, Konczack F, Olive D, Bonneville M, Breathnach R, Scotet E. The juxtamembrane domain of butyrophilin BTN3A1 controls phosphoantigen-mediated activation of human Vγ9Vδ2 T cells. J Immunol. (2017)
– Boutin L, Scotet E. Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells. Front Immunol. (2018)
– Joalland N*, Chauvin C*, Oliver L, Vallette FM, Pecqueur C, Jarry U, Scotet E. IL-21 Increases the Reactivity of Allogeneic Human Vγ9Vδ2 T Cells Against Primary Glioblastoma Tumors. J Immunother. (2018) *: co-authors
– Jarry U*, Joalland N*, Chauvin C*, Clémenceau B, Pecqueur C, Scotet E. Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts. J Vis Exp. (2018) *: co-authors

Human Monoclonal Antibodies
– Ouisse LH, Gautreau-Rolland L, Devilder MC, Osborn M, Moyon M, Visentin J, Halary F, Bruggemann M, Buelow R, Anegon I, Saulquin X. Antigen-specific single B cell sorting and expression-cloning from immunoglobulin humanized rats: a rapid and versatile method for the generation of high affinity and discriminative human monoclonal antibodies. BMC Biotechnol. (2017) http://www.hal.inserm.fr/inserm-01444749
– Devilder MC, Moyon M, Saulquin X*, Gautreau-Rolland L*. Generation of discriminative human onoclonal antibodies from rare antigen-specific B cells circulating in blood. J Vise Exp. (2018) *: corresponding authors http://www.hal.inserm.fr/inserm-01745629

Team 1

Contact

  • Emmanuel Scotet
  • Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
  • Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1
  • +33 2 28 08 02 23
  • emmanuel.scotet@inserm.fr

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