Going round in Circles. A new regulatory cell to control autoimmunity

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We have always had regulatory cells that control immune responsiveness. After the CD8 suppressor came the anergic cells, then CD4 Th1 and Th2 cells, then CD4 T regulatory cells and B regulatory cells made a brief appearrence. However, it looks like we are coming full circle and CD8 are back. A few years ago we could see that CD52 depletion was blocking immunological tolerance formation and it appears that this is controlled by a CD8 suppressor cell….This would imply that depleting CD8 T cells may not be a good thing. But as CD8 T cells were the dominant T cell in MS lesions, it is an obvious candidate for treatment with a specifc CD8 depleting antibody.

If we look back in history it was suggested that Kir (Kir4.1) was a target factor for autoimmunity in MS. It was said that most people with MS had antibodies targeting Kir….This Kir was a potassium channel but as essentially no-one could repeat the study, interest in Kir dropped. In this new study the new CD8 T cell is Kir positive, but this Kir means killer cell immunoglobulin-like receptors (KIRs) which can deliver an inhibitory signal. These cells are elevated in MS and COVID-19. It is reported that these cells suppress pathogenic T cells in autoimmune and infectious diseases. CD8 suppressor cells were reported years ago first in the 1970s, not the 1990s,

Although it was previously accepted that most self-specific T cells were eliminated in the thymus, many such cells survive and populate the periphery. It was hypothesized that this occurs because the threat of infectious diseases necessitates a complete T cell repertoire such that even self-reactive T cells might be needed in the response to a particular pathogen and are generated to suppress autoimmune responses that could arise during infection.

These cells will get depleted by alemtuzumab. Is this a reason why autoimmunity develops. I don’t know I guess we need to look and see what happens

Li et al. T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
Science 2022 • DOI: 10.1126/science.abi9591

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MouseDoctor

1 comment

  • Great coincidence just read the wikipedia page about KIR

    If i understand its basically Nk cells receptor and also some tcells

    Not well understood the inibitory and activation off this receptor

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