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Antigen Presenting B Cells Facilitate CD4 T Cell Cooperation Resulting in Enhanced Generation of Effector and Memory CD4 T Cells
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Antigen Presenting B Cells Facilitate CD4 T Cell Cooperation Resulting in Enhanced Generation of Effector and Memory CD4 T Cells
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Journal Article
Antigen Presenting B Cells Facilitate CD4 T Cell Cooperation Resulting in Enhanced Generation of Effector and Memory CD4 T Cells
2013
Overview
We show that the in vivo generation of cytokine-producing CD4 T cells specific for a given major histocompatibility class-II (MHCII)-binding peptide of hen egg lysozyme (HEL) is facilitated when mice are immunized with splenic antigen presenting cells (APC) pulsed with this HEL peptide and another peptide that binds a different MHCII molecule. This enhanced generation of peptide-specific effector CD4 T cells requires that the same splenic APC be pulsed with both peptides. Pulsed B cells, but not pulsed dendritic cells (DCs), can mediate CD4 T cell cooperation, which can be blocked by disrupting OX40-OX40L (CD134-CD252) interactions. In addition, the generation of HEL peptide-specific CD4 T cell memory is greater when mice are primed with B cells pulsed with the two peptides than with B cells pulsed with the HEL- peptide alone. Based on our findings, we suggest CD4 T cell cooperation is important for vaccine design, underlies the phenomenon of \"epitope-spreading\" seen in autoimmunity, and that the efficacy of B cell-depletion in the treatment of human cell-mediated autoimmune disease is due to the abrogation of the interactions between autoimmune CD4 T cells that facilitates their activation.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antigen Presentation - immunology
/ Antigen-Presenting Cells - cytology
/ Antigen-Presenting Cells - immunology
/ Antigens
/ B cells
/ CD4-Positive T-Lymphocytes - cytology
/ Chickens
/ Dendritic Cells - immunology
/ Epitopes
/ Female
/ Humans
/ Immunologic Memory - immunology
/ Lymphocyte Activation - immunology
/ Lysozyme
/ Mice
/ Muramidase - administration & dosage
/ Ovalbumin - administration & dosage
/ Peptides
/ Proteins
/ Receptors, OX40 - metabolism
/ Spleen
/ T cells
