Wednesday 31 July 2019

How t cells are transiently retained and controlled in their trafficking through the lymph nodes

How t cells are transiently retained and controlled in their trafficking through the lymph nodes.

T cell receptors recognise foreign antigens, then convey the message to the nucleus to induce a response.  The body produces many T cells, each with specific TCRs on its surface through the recombination of the genes that encode the receptors, before it has encountered complementary antigens.  By having a surplus of T cells carrying different TCRs, the body is able to mount a fast response once an intruder is detected.  Furthermore, there are thousands of identical TCRs on the surface of a T cell, which increases the likelihood of binding when an antigen is encountered.  The antigens that TCRs bind are small peptide fragments, or epitopes, displayed by MHC molecules on the surface of cells.  Cytotoxic T lymphocyte TCRs recognise epitopes displayed by MHC class I molecules on the surface of almost every cell in the body, so it can distinguish between ‘self’-antigens and foreign antigens (viral-infected cells), as well as being sensitive to the amount of self-antigen presented (increased number of self-antigens in malignant cells).  Helper T cell and inflammatory T cell TCRs recognise epitopes displayed by MHC class II molecules on the surface of antigen-presenting immune cells, including:  macrophages that engulf foreign particles such as bacteria; dendritic cells that present antigen to T cells; and B cells that produce antibodies.  The binding of the epitope to the TCR involves a T cell surface glycoprotein:  CD8 on cytotoxic T lymphocytes, and CD4 on helper T cells and inflammatory T cells (as shown in the picture to the left).  The CD8 and CD4 surface glycoproteins recognise MHC class I and II molecules, respectively.  The binding of a TCR to an epitope can result in a signal being sent to the nucleus to induce a response.

T cell migration within and between peripheral tissues and secondary lymphoid organs is essential for proper functioning of adaptive immunity. While active T cell migration within a tissue is fairly slow, blood vessels and lymphatic vessels (LVs) serve as speedy highways that enable T cells to travel rapidly over long distances. The molecular and cellular mechanisms of T cell migration out of blood vessels have been intensively studied over the past 30 years. By contrast, less is known about T cell trafficking through the lymphatic vasculature. This migratory process occurs in one manner within lymph nodes (LNs), where recirculating T cells continuously exit into efferent lymphatics to return to the blood circulation. In another manner, T cell trafficking through lymphatics also occurs in peripheral tissues, where T cells exit the tissue by means of afferent lymphatics, to migrate to draining LNs and back into blood. In this review, we highlight how the anatomy of the lymphatic vasculature supports T cell trafficking and review current knowledge regarding the molecular and cellular requirements of T cell migration through LVs

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