Chronic Experimental Colitis Induction of Mucosal Inflammation in CTLA-4 Control Tolerance or B7 Interactions with CD28 and (original) (raw)
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Chronic experimental colitis involves dysregulation of T cell responses, playing a crucial role in inflammatory bowel diseases like Crohn's disease and ulcerative colitis. B7 molecules, interacting with CD28 and CTLA-4, are essential in mediating T cell activation and tolerance. Blocking anti-B7.1 treatment prevents mucosal inflammation, whereas anti-CTLA-4 treatment exacerbates this condition. Understanding these interactions is vital for developing therapies aimed at modulating immune responses in IBD.
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Activation via the T lymphocyte cell surface molecule CD28 provides a potent amplification signal for interleukin 2 (IL-2) production in several in vitro systems. The B lymphocyte activation antigen, B7/BB1, is a natural ligand for CD28. Here we investigate the role of CD28 and B7/BB1 in primary activation of CD4+ T lymphocytes stimulated with allogeneic B lymphoblastoid cell lines. A subset of peripheral CD4+ T cells that is unresponsive to crosslinking of CD3/T cell receptor (TCR) with CD3 monoclonal antibody (mAb) does proliferate in response to allogeneic B lymphoblasts. TCR binding to allogeneic major histocompatibility complex antigens was an absolute requirement for activation of these cells because mAbs to either CD3 or human histocompatibility leukocyte antigen (HLA) class II completely inhibited activation. CD28 and B7/BB1 antibodies inhibited T cell proliferation 90% and 84%, respectively. Similar results were obtained with the total CD4+ T lymphocyte population. Crosslin...
The Journal of Immunology, 2001
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