Abstract
B cells, but not T cells, are considered to be important for the formation of follicular dendritic cell (FDC) clusters. Stimulation with agonist mAbs against CD137 (4-1BB), a TNFR family member primarily expressed on activated T cells, was effective in promoting T cell responses, but paradoxically suppressed T-dependent humoral immunity and autoantibody production in autoimmune disease models. Our present study shows that agonistic anti-CD137 treatment activates T cells, resulting in diminished FDC networks in B cell follicles, which are important components in T-dependent humoral immune responses both before and after the initiation of an immune response. Pretreatment with anti-CD137 before the secondary immunization inhibited memory Ab responses. Interestingly, CD137 costimulation-induced diminishment of FDC is T cell dependent. In addition, both CD4(+) and CD8(+) T cells are recruited into FDC area and are able to regulate FDCs by CD137 costimulation through a direct or indirect mechanism. These studies have revealed a previously unappreciated role of T cells in the regulation of FDC networks.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, CD / physiology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Dendritic Cells, Follicular / cytology*
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Dendritic Cells, Follicular / immunology*
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Dendritic Cells, Follicular / metabolism
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Down-Regulation / immunology
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Germinal Center / cytology
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Germinal Center / immunology
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Germinal Center / pathology
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Growth Inhibitors / immunology
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Growth Inhibitors / metabolism
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Growth Inhibitors / physiology
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Immunization, Secondary
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Immunoglobulin G / metabolism
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Immunologic Memory / genetics
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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Mice, Transgenic
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Nerve Growth Factor / antagonists & inhibitors
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Receptors, Nerve Growth Factor / immunology
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Receptors, Nerve Growth Factor / metabolism
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Receptors, Nerve Growth Factor / physiology*
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
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Tumor Necrosis Factor Receptor Superfamily, Member 9
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Growth Inhibitors
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Immunoglobulin G
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Tnfrsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 9