Investigators characterized the role of T cell immunoglobulin and mucin domain containing 3 (TIM-3) in restimulation-induced cell death regulation.
[Cell Death & Disease]
6445218 {6445218:VIZNVESE} apa 50 1 161255 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-d54920361676d08d1024b6845ba2c766%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22VIZNVESE%22%2C%22library%22%3A%7B%22id%22%3A6445218%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Lake%20et%20al.%22%2C%22parsedDate%22%3A%222021-04-14%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELake%2C%20C.%20M.%2C%20Voss%2C%20K.%2C%20Bauman%2C%20B.%20M.%2C%20Pohida%2C%20K.%2C%20Jiang%2C%20T.%2C%20Dveksler%2C%20G.%2C%20%26amp%3B%20Snow%2C%20A.%20L.%20%282021%29.%20TIM-3%20drives%20temporal%20differences%20in%20restimulation-induced%20cell%20death%20sensitivity%20in%20effector%20CD8%20%2B%20T%20cells%20in%20conjunction%20with%20CEACAM1.%20%3Ci%3ECell%20Death%20%26amp%3B%20Disease%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%284%29%2C%201%26%23x2013%3B17.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41419-021-03689-6%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41419-021-03689-6%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445218%26amp%3Bitem_key%3DVIZNVESE%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22TIM-3%20drives%20temporal%20differences%20in%20restimulation-induced%20cell%20death%20sensitivity%20in%20effector%20CD8%20%2B%20T%20cells%20in%20conjunction%20with%20CEACAM1%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Camille%20M.%22%2C%22lastName%22%3A%22Lake%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kelsey%22%2C%22lastName%22%3A%22Voss%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bradly%20M.%22%2C%22lastName%22%3A%22Bauman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Katherine%22%2C%22lastName%22%3A%22Pohida%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Timothy%22%2C%22lastName%22%3A%22Jiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gabriela%22%2C%22lastName%22%3A%22Dveksler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrew%20L.%22%2C%22lastName%22%3A%22Snow%22%7D%5D%2C%22abstractNote%22%3A%22Immune%20homeostasis%20depends%20upon%20effective%20clearance%20of%20pathogens%20while%20simultaneously%20preventing%20autoimmunity%20and%20immunopathology%20in%20the%20host.%20Restimulation-induced%20cell%20death%20%28RICD%29%20is%20one%20such%20mechanism%20where%20by%20activated%20T%20cells%20receive%20subsequent%20antigenic%20stimulation%2C%20reach%20a%20critical%20signal%20threshold%20through%20the%20T%20cell%20receptor%20%28TCR%29%2C%20and%20commit%20to%20apoptosis.%20Many%20details%20of%20this%20process%20remain%20unclear%2C%20including%20the%20role%20of%20co-stimulatory%20and%20co-inhibitory%20proteins%20that%20influence%20the%20TCR%20signaling%20cascade.%20Here%20we%20characterize%20the%20role%20of%20T%20cell%20immunoglobulin%20and%20mucin%20domain%20containing%203%20%28TIM-3%29%20in%20RICD%20regulation.%20TIM-3%20protected%20newly%20activated%20CD8%2B%20effector%20T%20cells%20from%20premature%20RICD%20during%20clonal%20expansion.%20Surprisingly%2C%20however%2C%20we%20found%20that%20TIM-3%20potentiated%20RICD%20in%20late-stage%20effector%20T%20cells.%20The%20presence%20of%20TIM-3%20increased%20proximal%20TCR%20signaling%20and%20proapoptotic%20protein%20expression%20in%20late-stage%20effector%20T%20cells%2C%20with%20no%20consistent%20signaling%20effects%20noted%20in%20newly%20activated%20cells%20with%20or%20without%20TIM-3.%20To%20better%20explain%20these%20differences%20in%20TIM-3%20function%20as%20T%20cells%20aged%2C%20we%20characterized%20the%20temporal%20pattern%20of%20TIM-3%20expression%20in%20effector%20T%20cells.%20We%20found%20that%20TIM-3%20was%20expressed%20on%20the%20surface%20of%20newly%20activated%20effector%20T%20cells%2C%20but%20remained%20largely%20intracellular%20in%20late-stage%20effector%20cells.%20Consistent%20with%20this%2C%20TIM-3%20required%20a%20ligand%20to%20prevent%20early%20RICD%2C%20whereas%20ligand%20manipulation%20had%20no%20effects%20at%20later%20stages.%20Of%20the%20known%20TIM-3%20ligands%2C%20carcinoembryonic%20antigen%5Cu2010related%20cell%20adhesion%20molecule%20%28CEACAM1%29%20showed%20the%20greatest%20difference%20in%20surface%20expression%20over%20time%20and%20also%20protected%20newly%20activated%20cells%20from%20premature%20RICD%2C%20with%20no%20measurable%20effects%20in%20late-stage%20effectors.%20Indeed%2C%20CEACAM1%20enabled%20TIM-3%20surface%20expression%20on%20T%20cells%2C%20implying%20a%20co-dependency%20for%20these%20proteins%20in%20protecting%20expanding%20T%20cells%20from%20premature%20RICD.%20Our%20findings%20suggest%20that%20co-signaling%20proteins%20like%20TIM-3%20and%20CEACAM1%20can%20alter%20RICD%20sensitivity%20at%20different%20stages%20of%20the%20effector%20T%20cell%20response%2C%20with%20important%20implications%20for%20checkpoint%20blockade%20therapy.%22%2C%22date%22%3A%222021-04-14%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41419-021-03689-6%22%2C%22ISSN%22%3A%222041-4889%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41419-021-03689-6%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-04-16T06%3A52%3A55Z%22%7D%7D%5D%7D
Lake, C. M., Voss, K., Bauman, B. M., Pohida, K., Jiang, T., Dveksler, G., & Snow, A. L. (2021). TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8 + T cells in conjunction with CEACAM1. Cell Death & Disease, 12(4), 1–17. https://doi.org/10.1038/s41419-021-03689-6 Cite