NDLI: Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells.

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Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells.

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Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pettigrew, Gavin J. Rehakova, Sylvia Negus, Margaret C. Bradley, J. Andrew Cole, Jennifer L. Bolton, Eleanor M. Saeb-Parsy, Kourosh Callaghan, Chris J. Qureshi, M. Saeed Conlon, Thomas M. Motallebzadeh, Reza
Description	Country affiliation: United kingdom Author Affiliation: Conlon TM ( Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK.)
Abstract	The durable alloantibody responses that develop in organ transplant patients indicate long-lived plasma cell output from T-dependent germinal centers (GCs), but which of the two pathways of CD4 T cell allorecognition is responsible for generating allospecific T follicular helper cells remains unclear. This was addressed by reconstituting T cell-deficient mice with monoclonal populations of TCR-transgenic CD4 T cells that recognized alloantigen only as conformationally intact protein (direct pathway) or only as self-restricted allopeptide (indirect pathway) and then assessing the alloantibody response to a heart graft. Recipients reconstituted with indirect-pathway CD4 T cells developed long-lasting IgG alloantibody responses, with splenic GCs and allospecific bone marrow plasma cells readily detectable 50 d after heart transplantation. Differentiation of the transferred CD4 T cells into T follicular helper cells was confirmed by follicular localization and by acquisition of signature phenotype. In contrast, IgG alloantibody was not detectable in recipient mice reconstituted with direct-pathway CD4 T cells. Neither prolongation of the response by preventing NK cell killing of donor dendritic cells nor prior immunization to develop CD4 T cell memory altered the inability of the direct pathway to provide allospecific B cell help. CD4 T cell help for GC alloantibody responses is provided exclusively via the indirect-allorecognition pathway.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1102830
Journal	The Journal of Immunology
Issue Number	6
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-03-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Germinal Center Immunology Isoantibodies Lymphocyte Activation T-lymphocytes, Helper-inducer Transplantation Immunology Animals Cell Differentiation Cell Separation Flow Cytometry Fluorescent Antibody Technique Cytology Immunohistochemistry Biosynthesis Lymphocyte Depletion Mice Mice, Inbred Balb C Mice, Knockout Mice, Transgenic Transplantation, Homologous Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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