Integrative T cell Immunobiology

Coordinators : J. van Meerwijk and O. Joffre

Scientific objectives

Our team uses an integrative biology approach to decipher the mechanisms that control, in a cell-autonomous or non-autonomous manner, intrathymic and peripheral differentiation of CD4 T cells.

The mechanisms involved in the development of T cells in the thymus also cause the generation of autospecific and therefore potentially dangerous T cells. To avoid autoimmune pathology, immune-tolerance needs to be established. The group led by Prof. Joost van Meerwijk, Professor at the Toulouse University and TMIT, studies development of regulatory T cells, key-players of immune-tolerance, in the thymus.

Depending on the nature and strength of the signals delivered by the antigen-presenting cells and the surrounding tissues, T lymphocytes mobilize different networks of transcription factors to induce distinct developmental programs that coordinate the acquisition of lineage-specific and danger-adapted phenotypes and functions. This differentiation is controlled and stabilised by epigenetic mechanisms. The group led by Dr. Olivier Joffre, associate professor at the Toulouse University, characterises the mechanisms controlling T cell fate and plasticity at the level of the chromatin.

Foxp3 regulatory T cells play a major role in the control chronic inflammatory diseases and auto-immune diseases and they inhibit anti-tumor immunity. The group led by Dr. Benoit Salomon, research director at Inserm who joined the team in 2022, studies the biology of regulatory T cells in peripheral tissues at homeostasis and in contexts of auto-immune diseases and cancers.

Our Projects

We study how T cell mediated immune tolerance develops in the thymus
The regulatory T cell repertoire is autospecific

In accordance with one of their main functions, we were the first to demonstrate that the repertoire of regulatory T cells is enriched in autospecific cells. This allows these cells to be activated when and where also the very dangerous autospecific T cells that cause autoimmunity are activated.

How does the thymus limit development of regulatory T cells?

The number of regulatory T cells developing in the thymus is much lower than the number of precursors with appropriate antigen-specificity. This suggests that the thymus somehow limits differentiation of regulatory T cells. We showed that limiting the number of precursors does not increase the proportion of cells differentiating into the regulatory lineage, which suggests that precursors are involved in shaping the niche.

Paradoxically increased development of regulatory T cells in autoimmune-prone mice

Regulatory T cells protect us from autoimmune pathology. Our finding that in autoimmune-prone mice more of these cells develop was therefore very surprising. Data from our lab also showed genetic control of the development of regulatory T cells. One involved locus is closely linked to the major histocompatibility locus (MHC).

Regulatory T cells migrate back to the thymus

We demonstrated that regulatory T cells activated during immune-responses migrate back to the thymus and influence induction of immune-tolerance. We are currently working on further consequences

of this intriguing phenomenon.

We characterize the epigenetic mechanisms controlling T cell fate

The integrity of the organism is ensured by a tight interplay between conventional and regulatory T cells. The intercellular and environmental signals regulating their programming and crosstalk and the signalling events and transcriptional networks they induce have been extensively characterized. However, we now know that T cell identity is also largely controlled at the epigenetic level. The group led by Dr. Olivier Joffre, associate professor at the Toulouse University and holder of an interface contract with the Inserm, characterises the epigenetic mechanisms controlling T cell fate. It deciphers the role of non-coding RNAs and of several chromosomal proteins in the response of conventional and regulatory T cells to environmental signals and in the interplay between these two populations of cells.



We study the biology of regulatory T cells in order to develop new immunotherapies

The projects of the group led by Dr. Benoit Salomon aim to better understand the biology of Foxp3 regulatory T cells (Tregs) in homeostasis and the mechanisms involving Tregs in the control of autoimmune diseases and anti-tumor responses. These projects are organized around 4 axes. 1- Study of the biology and function of “ex-Tregs”, a population of conventional T lymphocytes which have been Tregs at some time in their life and have lost this status. 2- Study of the metabolic adaptation of Tregs in non-lymphoid tissues. 3- Study of the mechanisms of Treg mediated suppression in autoimmune diseases and cancers involving molecules of the TNF family. 4- Study of new therapeutic approaches to these diseases involving Tregs.


Most of these projects are carried out using genetically modified mice in which the expression of a gene of interest is eliminated specifically in Tregs. We thus generated conditional KO mice for receptors of the TNF family (TNFR2, 4-1BB), co-stimulatory molecules (ICOS) or molecules regulating cell metabolism (AMPK, LKB1). As a reference model of autoimmune diseases, we use experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. These projects notably require the use of multiparametric flow cytometry and transcriptomics technology.

Portfolio modèles animaux



Other information



Apert, Cécile; Galindo-Albarrán, Ariel; Castan, Sarah; Detraves, Claire; Michaud, Héloise; McJannett, Nicola; Haegeman, Bart; Fillatreau, Simon; Malissen, Bernard; Hollander, Georg; Zuklys, Saulius; Santamaria, Jérémy; Joffre, Olivier; Romagnoli, Paola; van Meerwijk, Joost

IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes Journal Article

Frontiers in Immunology, 2022.

Abstract | Links | BibTeX


Galindo-Albarran Ariel; Castan, Sarah; Santamaria Jérémy; Joffre Olivier; Haegeman Bart; Romagnoli Paola; Van Meerwijk Joost

The Repertoire of Newly Developing Regulatory T Cells in the Type 1 Diabetes-Prone NOD Mouse Is Very Diverse Journal Article

Diabetes, 70 (8), pp. 1729-1737, 2021, ISSN: 1939-327X.

Abstract | Links | BibTeX

Darrigues, Julie ; Santamaria, Jeremy C; Galindo-Albarrán, Ariel ; Robey, Ellen A; Joffre, Olivier P; van Meerwijk, Joost P M; Romagnoli, Paola

Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells Journal Article

European Journal of Immunology, 2021, ISSN: 15214141.

Abstract | Links | BibTeX


Maqbool, Muhammad Ahmad ; Pioger, Léo; El Aabidine, Amal Zine ; Karasu, Nezih ; Molitor, Anne Marie ; Dao, Lan T M; Charbonnier, Guillaume ; van Laethem, Francois ; Fenouil, Romain ; Koch, Frederic ; Lacaud, Georges ; Gut, Ivo ; Gut, Marta ; Amigorena, Sebastian ; Joffre, Olivier ; Sexton, Thomas ; Spicuglia, Salvatore ; Andrau, Jean Christophe

Alternative Enhancer Usage and Targeted Polycomb Marking Hallmark Promoter Choice during T Cell Differentiation Journal Article

Cell Reports, 32 (7), 2020, ISSN: 22111247.

Abstract | Links | BibTeX

Adoue, Véronique ; Joffre, Olivier

Endogenous retroviruses: Friend or foe of the immune system? Journal Article

Médecine/Sciences, 36 (3), pp. 253-260, 2020, ISSN: 19585381.

Abstract | Links | BibTeX


Gehrmann, Ulf ; Burbage, Marianne ; Zueva, Elina ; Goudot, Christel ; Esnault, Cyril ; Ye, Mengliang ; Carpier, Jean Marie ; Burgdorf, Nina ; Hoyler, Thomas ; Suarez, Guadalupe ; Joannas, Leonel ; Heurtebise-Chrétien, Sandrine ; Durand, Sylvère ; Panes, Rébecca ; Bellemare-Pelletier, Angélique ; Sáez, Pablo J; Aprahamian, Fanny ; Lefevre, Deborah ; Adoue, Veronique ; El Aabidine, Amal Zine ; Ahmad, Maqbool Muhammad ; Hivroz, Claire ; Joffre, Olivier ; Cammas, Florence ; Kroemer, Guido ; Gagnon, Etienne ; Andrau, Jean Christophe ; Amigorena, Sebastian

Critical role for TRIM28 and HP1$beta$/$gamma$ in the epigenetic control of T cell metabolic reprograming and effector differentiation Journal Article

Proceedings of the National Academy of Sciences of the United States of America, 116 (51), pp. 25839–25849, 2019, ISSN: 10916490.

Abstract | Links | BibTeX

Adoue, V; Binet, B; Malbec, A; Fourquet, J; Romagnoli, P; van Meerwijk, J P M; Amigorena, S; Joffre, O P

The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses. Journal Article

Immunity, 50 , pp. 629–644, 2019.

Abstract | Links | BibTeX


Santamaria, J; Darrigues, J; van Meerwijk, J P M; Romagnoli, P

Antigen-presenting cells and T-lymphocytes homing to the thymus shape T cell development Journal Article

Immunol Lett, 204 , pp. 9-15, 2018, ISSN: 0165-2478.

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Araujo Furlan, C L; Tosello Boari, J; Rodriguez, C; Canale, F P; Fiocca Vernengo, F; Boccardo, S; Beccaria, C G; Adoue, V; Joffre, O; Gruppi, A; Montes, C L; Acosta Rodriguez, E V

Limited Foxp3(+) Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8(+) T Cell Immunity Journal Article

Front Immunol, 9 , pp. 2555, 2018, ISSN: 1664-3224.

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Apert, C; Romagnoli, P; van Meerwijk, J P M

IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes Journal Article

Protein Cell, 2017, ISSN: 1674-800x.

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Darrigues, J; van Meerwijk, J P M; Romagnoli, P

Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review Journal Article

Gerontology, 2017, ISSN: 0304-324x.

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Vuddamalay, Y; van Meerwijk, J P M

CD28neg and CD28low CD8+ regulatory T cells: Of Mice and Men Journal Article

Frontiers in immunology, doi: 10.3389/fimmu.2017.00031 , 2017.



Decque, A *; Joffre, O *; Magalhaes, J G *; Cossec, J C *; Blecher-Gonen, R; Lapaquette, P; Silvin, A; Manel, N; Joubert, P E; Seeler, J S; Albert, M L; Amit, I; Amigorena, S; Dejean, A

Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing Journal Article

Nat Immunol, 17 (2), pp. 140-9, 2016, ISSN: 1529-2908.

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Vuddamalay, Y; Attia, M; Vicente, R; Pomie, C; Enault, G; Leobon, B; Joffre, O; Romagnoli, P; van Meerwijk, J P

Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus Journal Article

Immunology, 148 (2), pp. 187-96, 2016, ISSN: 1365-2567 (Electronic) 0019-2805 (Linking).

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Hamdi, Y; Soucy, P; Adoue, V; Michailidou, K; Canisius, S; Lemaçon, A; Droit, A; Andrulis, I L; Anton-Culver, H; Arndt, V; Baynes, C; Blomqvist, C; Bogdanova, N V; Bojesen, S E; Bolla, M K; Bonanni, B; Borresen-Dale, AL ; Brand, J S; Brauch, H; Brenner, H; Broeks, A; Burwinkel, B; Chang-Claude, J; Couch, F J; Cox, A; Cross, S S; Czene, K; Darabi, H; Dennis, J; Devilee, Pr ; Dörk, T; Dos-Santos-Silva, I; Eriksson, M; Fasching, P A; Figueroa, J; Flyger, H; Garcia-Closas, M; Giles, G G; Goldberg, M S; Gonzalez-Neira, A; Grenaker-Alnaes, G; Guénel, P; Haeberle, L; Haiman, C A; Hamann, U; Hallberg, E; Hooning, M J; Hopper, J L; Jakubowska, A; Jones, M; Kabisch, M; Kataja, V; Lambrechts, D; Le Marchand Land Lindblom, A; Lubinski Jand Mannermaa, A; Maranian, M; Margolin, S; Marme, F; Milne, R L; Neuhausen, S L; Nevanlinna, H; Neven, P; Olswold, C; Peto, J; Plaseska-Karanfilska, D; Pylkäs, K; Radice, P; Rudolph, A; Sawyer, E J; Schmidt, M K; Shu, X O; Southey, M C; Swerdlow, A; Tollenaar, R A E M; Tomlinson, I; Torres, D; Truong, T; Vachon, C; Van Den Ouweland, A M W; Wang, Q; Winqvist, R; Zheng, W; Benitez, J; Chenevix-Trench, G; Dunning, A M; Pharoah, P D P; Kristensen, V; Hall, P; Easton, D F; Pastinen, T; Nord, S; Simard, J

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21 Journal Article

Oncotarget, 2016, ISSN: 19492553.

Abstract | Links | BibTeX


Thiault, N; Darrigues, J; Adoue, V; Gros, M; Binet, B; Perals, C; Leobon, B; Fazilleau, N; Joffre, O P; Robey, E A; van Meerwijk, J P M; Romagnoli, P

Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors Journal Article

Nature Immunol, 16 , pp. 628–634, 2015.

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Adoue, V; Schiavi, A; Light, N; Almlof, J C; Lundmark, P; Ge, B; Kwan, T; Caron, M; Ronnblom, L; Wang, C; Chen, S H; Goodall, A H; Cambien, F; Deloukas, P; Ouwehand, W H; Syvanen, A C; Pastinen, T

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs Journal Article

Molecular Systems Biology, 10 (10), pp. 754, 2014.

Abstract | Links | BibTeX

Light, N; Adoue, V; Ge, B; Chen, S-H; Kwan, T; Pastinen, T

Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping. Journal Article

Epigenetics, 9 (9), pp. 1238–1251, 2014.

Abstract | Links | BibTeX


Pasquet, L; Douet, J Y; Sparwasser, T; Romagnoli, P; van Meerwijk, J P M

Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells Journal Article

Blood, 121 (21), pp. 4303-10, 2013, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

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Tellier, J; Andrianjaka, A; Vicente, R; Thiault, N; Enault, G; Garchon, H J; van Meerwijk, J P M; Romagnoli, P

Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility Journal Article

Eur J Immunol, 43 (5), pp. 1356-62, 2013, ISSN: 1521-4141 (Electronic) 0014-2980 (Linking).

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Romagnoli, P; Dooley, J; Enault, G; Vicente, R; Malissen, B; Liston, A; van Meerwijk, J P M

The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes Journal Article

Journal of Immunology, 189 (8), pp. 3831-7, 2012, ISSN: 1550-6606 (Electronic) 0022-1767 (Linking).

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Nouzé, C; Pasquet, L; van Meerwijk, J P M

In vitro expansion of alloantigen-specific regulatory T cells and their use in prevention of allograft-rejection Book Chapter

Kassiotis, G; Liston, A (Ed.): Regulatory T-Cells: Methods and Protocols, 707 , pp. 187-196, Springer, 2011.


Pasquet, Lise ; Joffre, Olivier ; Santolaria, Thibault ; van Meerwijk, Joost

Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells Journal Article

Frontiers in Immunology, 2 , 2011, ISSN: 1664-3224.

Links | BibTeX

Pomie, C; Vicente, R; Vuddamalay, Y; Ardesjö Lundgren, B; van der Hoek, M; Enault, G; Kagan, J; Fazilleau, N; Scott, H S; Romagnoli, P; van Meerwijk, J P M

AIRE-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis Journal Article

Proceedings of the National Academy of Sciences of the U.S.A., 108 (30), pp. 12437-12442, 2011.



Romagnoli, P; van Meerwijk, J P M

Thymic selection and lineage commitment of CD4+Foxp3+ regulatory T lymphocytes Journal Article

Prog Mol Biol Transl Sci., 92 , pp. 251-77, 2010.



Joffre, O; Santolaria, T; Calise, D; Al Saati, T; Hudrisier, D; Romagnoli, P; van Meerwijk, J P M

Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes Journal Article

Nature Medicine, 14 (1), pp. 88-92, 2008.


Joffre, O; Santolaria, T; van Meerwijk, J P M

[Tregs-based immunotherapy: an efficient way to fully inhibit acute and chronic rejection.] Journal Article

Med Sci (Paris), 24 (8-9), pp. 689-691, 2008, ISSN: 0767-0974 (Print).

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Pomie, C; Menager-Marcq, I; van Meerwijk, J P M

Murine CD8(+) regulatory T lymphocytes: The new era Journal Article

Hum Immunol, 69 , pp. 708-714, 2008, ISSN: 0198-8859 (Print).

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Romagnoli, P; Ribot, J; Tellier, J; van Meerwijk, J P M

Thymic and peripheral generation of CD4+Foxp3+ regulatory T cells Book Chapter

Jiang, S (Ed.): Regulatory T cells and clinical application, in press , Springer, 2008, ISBN: 978-0-387-77908-9.

Links | BibTeX


Ribot, J; Enault, G; Pilipenko, S; Huchencq, A; Calise, M; Hudrisier, D; Romagnoli, P; van Meerwijk, J P M

Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection Journal Article

J. Immunol., 179 , pp. 6741-6748, 2007.



Joffre, O; van Meerwijk, J P M

CD4+CD25+ regulatory T lymphocytes in bone marrow transplantation Journal Article

Seminars in Immunology, 18 (2), pp. 128-135, 2006.


Menager-Marcq, I; Pomie, C; Romagnoli, P; van Meerwijk, J P M

CD8+CD28- regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice Journal Article

Gastroenterology, 131 (6), pp. 1775-85, 2006.

Links | BibTeX

Ribot, J; Romagnoli, P; van Meerwijk, J P M

Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR-repertoire Journal Article

J. Immunol., 177 (2), pp. 1101-1107, 2006.


Tellier, J; van Meerwijk, J P M; Romagnoli, P

An MHC-linked locus modulates thymic differentiation of CD4+CD25+Foxp3+ regulatory T lymphocytes Journal Article

Int Immunol, 18 (11), pp. 1509-1519, 2006.

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Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Molecular signature of recent thymic selection events on effector and regulatory CD4+ T lymphocytes Journal Article

Journal of Immunology, 175 , pp. 5751-5758, 2005.


Romagnoli, P; Tellier, J; van Meerwijk, J P M

Genetic control of thymic development of CD4+CD25+FoxP3+ regulatory T lymphocytes Journal Article

Eur J Immunol, 35 , pp. 3525-3532, 2005.



Cannarile, M A; Decanis, N; van Meerwijk, J P; Brocker, T

The role of dendritic cells in selection of classical and nonclassical CD8+ T cells in vivo Journal Article

J Immunol, 173 (8), pp. 4799-805, 2004.

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Joffre, O; Gorsse, N; Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Induction of antigen-specific tolerance to bone-marrow allografts with CD4+CD25+ T lymphocytes Journal Article

Blood, 103 (11), pp. 4216-4221, 2004.

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Capone, M; Lees, R L; Finke, D; Ernst, B; van Meerwijk, J P M; MacDonald, H R

Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium. Journal Article

Eur J Immunol, 33 (6), pp. 1471-7, 2003.

Links | BibTeX

Cemerski, S; van Meerwijk, J P M; Romagnoli, P

Oxidative stress-induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial signaling molecules Journal Article

Eur J Immunol, 33 (8), pp. 2178-85, 2003.


Hudrisier, D; Feau, S; Bonnet, V; Romagnoli, P; van Meerwijk, J P M

In vivo maintenance of T lymphocyte unresponsiveness induced by thymic medullary epithelium requires antigen presentation by radioresistant cells Journal Article

Immunology, 108 , pp. 24-31, 2003.



Cemerski, S; Cantagrel, A; van Meerwijk, J P M; Romagnoli, P

Reactive oxygen species differentially affect T cell receptor signaling pathways Journal Article

Journal of Biological Chemistry, 277 , pp. 19585-19593, 2002.

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Constantin, A; Lauwers-Cances, V; Navaux, F; Abbal, M; van Meerwijk, J; Mazieres, B; Cambon-Thomsen, A; Cantagrel, A

Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a prospective longitudinal study Journal Article

J Rheumatol, 29 (1), pp. 15-20, 2002.

Links | BibTeX

Constantin, A; Lauwers-Cances, V; Navaux, F; Abbal, M; van Meerwijk, J; Mazieres, B; Cambon-Thomsen, A; Cantagrel, A

Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: Association with severity and progression of rheumatoid arthritis in a prospective study Journal Article

Arthritis Rheum, 46 (7), pp. 1754-62, 2002.

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Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Preferential recognition of self-antigens despite normal thymic deletion of CD4+CD25+ regulatory T cells Journal Article

Journal of Immunology, 168 , pp. 1644-1648, 2002.

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Romagnoli, P; Strahan, D; Pelosi, M; Cantagrel, A; van Meerwijk, J P M

A potential role for tyrosine kinase p56lck in rheumatoid arthritis synovial fluid T lymphocyte hyporesponsiveness Journal Article

International Immunology, 13 (3), pp. 305-312, 2001.


Impact on the society

A better understanding of the development of T lymphocytes and their differentiation upon aggression by pathogens or tumours will lead to development of more specific and effective innovating therapies against e.g. immunopathologies. The regulatory T cell-based therapy against allograft-rejection developed by our team is an excellent example.

The TMIT team is also much involved in immunology-teaching at the Toulouse University. Its members teach courses at distinct academic levels, direct the Master program in Immunology and Infectious Diseases, and train PhD-students.

Agence nationale de la recherche

Agence nationale de la recherche

Fondation de recherche médicale

Fondation de recherche médicale

Région Occitanie

Région Occitanie

Fondation ARC

Fondation ARC

Ligue contre le cancer

Ligue contre le cancer







Sanofi Genzyme

Sanofi Genzyme