Control of CD8 T cell proliferation and terminal differentiation by active STAT5 and CDKN2A/CDKN2B

Autor: Jacques A. Nunès, Magali Grange, Romain Roncagalli, Guylène Firaguay, Nathalie Auphan-Anezin, Anne-Marie Schmitt-Verhulst, Jacques Ghysdael, Amandine Mas, Marilyn Giordano
Přispěvatelé: Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nunès, Jacques
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Adoptive cell transfer
senescence
CD8-Positive T-Lymphocytes
MESH: Mice
Knockout
Mice
Interleukin 21
0302 clinical medicine
STAT5 Transcription Factor
Immunology and Allergy
Cytotoxic T cell
MESH: Animals
IL-2 receptor
Receptors
Immunologic
Cellular Senescence
transcription factor
Mice
Knockout
0303 health sciences
ZAP70
Cell Differentiation
MESH: Receptors
Antigen
T-Cell
MESH: Cyclin-Dependent Kinase Inhibitor p15
Natural killer T cell
MESH: CD8-Positive T-Lymphocytes
MESH: Gene Expression Regulation
Cell biology
MESH: Cell Aging
MESH: Cyclin-Dependent Kinase Inhibitor p16
[SDV.IMM]Life Sciences [q-bio]/Immunology
immunotherapy
MESH: Cell Differentiation
[SDV.IMM] Life Sciences [q-bio]/Immunology
Immunology
Receptors
Antigen
T-Cell
Biology
03 medical and health sciences
MESH: Cell Proliferation
Animals
Lectins
C-Type
Antigen-presenting cell
MESH: Receptors
Immunologic
MESH: Mice
Cyclin-Dependent Kinase Inhibitor p16
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p15
030304 developmental biology
Interleukin 3
MESH: STAT5 Transcription Factor
Original Articles
Gene Expression Regulation
Cancer research
effector CD8 T cell
gene regulation
030215 immunology
Zdroj: Immunology
Immunology, Wiley, 2015, 145 (4), pp.543-57. ⟨10.1111/imm.12471⟩
Immunology, 2015, 145 (4), pp.543-57. ⟨10.1111/imm.12471⟩
ISSN: 0019-2805
1365-2567
DOI: 10.1111/imm.12471⟩
Popis: International audience; CD8 T cells used in adoptive immunotherapy may be manipulated to optimize their effector functions, tissue-migratory properties and long-term replicative potential. We reported that antigen-stimulated CD8 T cells transduced to express an active form of the transcription factor signal transducer and activator of transcription 5 (STAT5CA) maintained these properties upon adoptive transfer. We now report on the requirements of STAT5CA-expressing CD8 T cells for cell survival and proliferation in vivo. We show that STAT5CA expression allows for greater expansion of T cells in vivo, while preserving dependency on T-cell-receptor-mediated tonic stimulation for their in vivo maintenance and return to a quiescent stage. STAT5CA expression promotes the formation of a large pool of effector memory T cells that respond upon re-exposure to antigen and present an increased sensitivity to γc receptor cytokine engagement for STAT5 phosphorylation. In addition, STAT5CA expression prolongs the survival of what would otherwise be short-lived terminally differentiated KLRG1-positive effector cells with up-regulated expression of the senescence-associated p16(INK) (4A) transcripts. However, development of a KLRG1-positive CD8 T cell population was independent of either p16(INK) (4A) or p19(ARF) expression (as shown using T cells from CDKN2A(-/-) mice) but was associated with expression of transcripts encoding p15(INK) (4B) , another protein involved in senescence induction. We conclude that T-cell-receptor- and cytokine-dependent regulation of effector T cell homeostasis, as well as mechanisms leading to senescent features of a population of CD8 T cells are maintained in STAT5CA-expressing CD8 T cells, even for cells that are genetically deficient in expression of the tumour suppressors p16(INK) (4A) and p19(ARF) .
Databáze: OpenAIRE
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