Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells.
J Immunol
; 188(6): 2643-52, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22323543
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunologia de Transplantes
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Ativação Linfocitária
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Linfócitos T Auxiliares-Indutores
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Centro Germinativo
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Isoanticorpos
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article