Immunity system complexity: how T cells develop, spread (Introduction)

by David Turell , Friday, December 10, 2021, 15:51 (1079 days ago) @ David Turell

Many T cells are tissue residents, not free floating in the circulation and have other functions than as killers:

https://www.science.org/doi/10.1126/science.abf0095

"Conventional T cells recognize peptides that are presented by polymorphic major histocompatibility complexes (MHCs). By contrast, many tissue-resident T cells, such as mucosal-associated invariant T cells, invariant natural killer T cells, and γδ T cells, respond to modified peptides and small molecules presented by conserved MHC-like molecules. Unconventional T cells are important for host defense and tissue repair and seed tissues during critical early-life windows of development.

"In addition to providing antimicrobial immunity, the immune system governs numerous aspects of host physiology, in part through the coordinated action of tissue-resident lymphocytes. Although conventional T cells recognize peptides presented by polymorphic major histocompatibility complexes (MHCs), a large proportion of T cells within tissues are specific for modified peptides and small molecules. These unconventional T cells are restricted by monomorphic MHC molecules, many of which exhibit a high level of conservation across species, suggesting an essential role for these cells throughout evolution. Some unconventional T cells express semi-invariant T cell receptors (TCRs) that limit their antigenic range analogously to innate immune receptors. Termed innate-like T cells, these populations developmentally acquire effector characteristics prior to thymic egress, including rapid cytokine release and expression of chemokine receptors and integrins. Without the necessity of antigen-mediated activation within secondary lymphoid organs, innate-like T cells accumulate within tissues earlier than conventional effector T cells. Consequently, recent work has shown that these unconventional T cells are particularly responsive to early-life signals and promote the maintenance of tissue homeostasis as a coordinated network.

"As a consequence of their emergence in early life, unconventional T cells contribute to the initial dialog between the host and the microbiota, on which some subsets depend for their development. Exposure to commensal microbes during the first weeks of life imprints the abundance of mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells in tissues, due to both TCR-mediated activation and modulation of tissue-specific chemokines. Epithelial cell expression of host molecules in early life is also necessary for the accumulation of a defined subset of γδ T cells. Absence of these early-life signals cannot be compensated for later in life and has long-lasting consequences for host physiology, rendering adult animals more susceptible to inflammation.....Although unconventional T cells exhibit overlapping roles, their disparate stratification within epithelial tissues suggests that each population may serve a unique purpose in maintaining tissue homeostasis. Animal models deficient in subsets of unconventional T cells exhibit compensatory increases of other unconventional T cells, indicating that these populations constitute a network of redundant cellular mechanisms that contribute to tissue resilience. However, inflammation can abrogate the expression of epithelial molecules that maintain a subset γδ T cells, resulting in a compensatory increase in more inflammatory γδ T cells that predispose the tissue to chronic inflammation."

Comment: the key to the importance of these cells is that they develop at birth and quickly learn to recognize and neutralize foreign proteins. Obviously, continuing to live without dangerous infections is a requirement for life and this system is designed for just that protection. The cells arrive at birth with this built-in ability. Unfortunately, improper inflammatory responses can happen as noted here and in our previous discussions. Much of this research is directed at finding correcting therapy.