Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling

• Published in: The Journal of immunology (1950) Vol. 175; no. 2; pp. 884 - 890
• Main Authors: Sun, Yonglian, Blink, Sarah E, Chen, Jonathan H, Fu, Yang-Xin
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2005
• Subjects: Adoptive Transfer; Animals; Antibodies, Monoclonal - administration & dosage; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, CD - physiology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Dendritic Cells, Follicular - cytology; Dendritic Cells, Follicular - immunology; Dendritic Cells, Follicular - metabolism; Down-Regulation - immunology; Germinal Center - cytology; Germinal Center - immunology; Germinal Center - pathology; Growth Inhibitors - immunology; Growth Inhibitors - metabolism; Growth Inhibitors - physiology; Immunization, Secondary; Immunoglobulin G - metabolism; Immunologic Memory - genetics; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - deficiency; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Nerve Growth Factor - antagonists & inhibitors; Receptors, Nerve Growth Factor - immunology; Receptors, Nerve Growth Factor - metabolism; Receptors, Nerve Growth Factor - physiology; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor - physiology; Signal Transduction - genetics; Signal Transduction - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; Tumor Necrosis Factor Receptor Superfamily, Member 9
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.2.884

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.