APRIL modulates B and T cell immunity

Jens V. Stein; Marta López-Fraga; Fernando A. Elustondo; Carla E. Carvalho-Pinto; Dolores Rodríguez; Ruth Gómez-Caro; Joan de Jong; Carlos Martínez-A; Jan Paul Medema; Michael Hahne

doi:10.1172/JCI15034

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APRIL modulates B and T cell immunity

Jens V. Stein, Marta López-Fraga, Fernando A. Elustondo, Carla E. Carvalho-Pinto, Dolores Rodríguez, Ruth Gómez-Caro, Joan de Jong, Carlos Martínez-A, Jan Paul Medema et Michael Hahne

The Journal of clinical investigation, Vol.109(12), pp.1587-1598

15/06/2002

DOI: https://doi.org/10.1172/JCI15034

PMID: 12070306

Résumé

The TNF-like ligands APRIL and BLyS are close relatives and share the capacity to bind the receptors TACI and BCMA. BLyS has been shown to play an important role in B cell homeostasis and autoimmunity, but the biological role of APRIL remains less well defined. Analysis of T cells revealed an activation-dependent increase in APRIL mRNA expression. We therefore generated mice expressing APRIL as a transgene in T cells. These mice appeared normal and showed no signs of B cell hyperplasia. Transgenic T cells revealed a greatly enhanced survival in vitro as well as enhanced survival of staphylococcal enterotoxin B–reactive CD4+ T cells in vivo, which both directly correlate with elevated Bcl-2 levels. Analysis of humoral responses to T cell–dependent antigens in the transgenic mice indicated that APRIL affects only IgM but not IgG responses. In contrast, T cell–independent type 2 (TI-2) humoral response was enhanced in APRIL transgenic mice. As TACI was previously reported to be indispensable for TI-2 antibody formation, these results suggest a role for APRIL/TACI interactions in the generation of this response. Taken together, our data indicate that APRIL is involved in the induction and/or maintenance of T and B cell responses.

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Titre: APRIL modulates B and T cell immunity
Créateurs - sans rôle: Jens V. Stein - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Marta López-Fraga - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Fernando A. Elustondo - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Carla E. Carvalho-Pinto - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Dolores Rodríguez - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Ruth Gómez-Caro - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Joan de Jong - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Carlos Martínez-A - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Jan Paul Medema - Leiden University Medical Center
Michael Hahne - Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnología, Madrid, Spain Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Détails de publication: The Journal of clinical investigation, Vol.109(12), pp.1587-1598
Éditeur: American Society for Clinical Investigation
Nombre de pages: 12
Identifiants: 99154037709311
Unité académique: Institut de Génétique Moléculaire de Montpellier - IGMM
Langue: English
Type de ressource: Journal article