T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship

Abstract

Co-ordinated interaction between distinct cell types is a hallmark of successful immune function. A striking example of this is the carefully orchestrated cooperation between helper T cells and B cells that occurs during the initiation and fine-tuning of T-cell dependent antibody responses. While these processes have evolved to permit rapid immune defense against infection, it is becoming increasingly clear that such interactions can also underpin the development of autoimmunity. Here we discuss a selection of cellular and molecular pathways that mediate T cell/B cell collaboration and highlight how in vivo models and genome wide association studies link them with autoimmune disease. In particular, we emphasize how CTLA-4-mediated regulation of CD28 signaling controls the engagement of secondary costimulatory pathways such as ICOS and OX40, and profoundly influences the capacity of T cells to provide B cell help. While our molecular understanding of the co-operation between T cells and B cells derives from analysis of secondary lymphoid tissues, emerging evidence suggests that subtly different rules may govern the interaction of T and B cells at ectopic sites during autoimmune inflammation. Accordingly, the phenotype of the T cells providing help at these sites includes notable distinctions, despite sharing core features with T cells imparting help in secondary lymphoid tissues. Finally, we highlight the interdependence of T cell and B cell responses and suggest that a significant beneficial impact of B cell depletion in autoimmune settings may be its detrimental effect on T cells engaged in molecular conversation with B cells.

Ten years of prevalence and clinical laboratory features of HCMV infected children in a hospital of Jiangsu Province

“…CMV reactivates and spreads to organs as well as immune cells including lymphocytes, monocytes and neutrophils to accomplish dissemination[18][19][20], when blood routine test result can reflect the systemic inflammatory and immune responses[21][22][23]. In this study, we collected blood routine test results of 971 hospitalized infants aged from 3 to 12 months and found that the absolute counts of peripheral leukocytes, monocytes, neutrophils and platelets were significantly decreased in CMV+ group.…”

Expression patterns of CD28 and CTLA‐4 in early, chronic, and untreated rheumatoid arthritis

“…Activation of T cells requires at first the binding of the T‐cell receptor (TCR) with a MHC‐peptide complex; however, after triggering of TCR, T‐cell activation is mediated by co‐stimulation signals, which are considered a crucial way to control a T lymphocyte‐mediated immune response and inflammatory reactions …”

“…CD28 and the cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) are the main costimulatory molecules, expressed both by CD4 + T cells and by CD8 + T cells, whose positive and negative signals, respectively, determine the outcome of the T‐cell response to foreign and self‐antigens . CD28 and CTLA‐4 are homologous and belong to the immunoglobulin superfamily, and both molecules interact with the same ligands B7‐1 (CD80) and B7‐2 (CD86) on antigen‐presenting cells (APCs) . CD28 is constitutively expressed on T cells and delivers an activation signal; on the other hand, CTLA‐4 transduces an inhibitory signal and it is only expressed on activated T cells …”

“…CD28 and CTLA‐4 are homologous and belong to the immunoglobulin superfamily, and both molecules interact with the same ligands B7‐1 (CD80) and B7‐2 (CD86) on antigen‐presenting cells (APCs) . CD28 is constitutively expressed on T cells and delivers an activation signal; on the other hand, CTLA‐4 transduces an inhibitory signal and it is only expressed on activated T cells …”

Mapping gene regulatory networks of primary CD4+T cells using single-cell genomics and genome engineering

“…Th 17 ) (1-4), signal and recruit B cells (e.g. Th 1 and Th 2 ) (5)(6)(7)(8)(9)(10)(11), and induce tolerance in the tissue microenvironment (e.g. T reg ) (12,13).…”