Activation-induced thrombospondin-4 works with thrombospondin-1 to build cytotoxic supramolecular attack particles

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(6)

Опубликована: Фев. 4, 2025

Cytotoxic attack particles released by CTLs and NK cells include diverse phospholipid membrane glycoprotein encapsulated entities that contribute to target cell killing. Supramolecular (SMAPs) are one type of particle characterized a cytotoxic core enriched in granzymes perforin surrounded proteinaceous shell including thrombospondin (TSP)-1. TSP-4 was also detected bulk analysis SMAPs CTLs; however, it has not been investigated whether contributes distinct SMAP types or the same as TSP-1 and, if SMAP, cooperate compete. Here, we observed expression increased upon CD8 + T activation while, surprisingly, down-regulated. Correlative Light Electron Microscopy Stimulated Emission Depletion microscopy localized SMAP-containing multicore granules. Superresolution dSTORM revealed usually while with single-positive shells rare. Retention Using Selective Hooks assays showed localizes lytic granules faster than promotes its accumulation therein. contributed direct CTL-mediated killing, previously shown for TSP-1. were both required latent SMAP-mediated which kill targets after removal CTLs. Of note, found chronic lymphocytic leukemia (CLL) culture supernatants suppressed CTL These results identify functionally important component suggest may be targeted immune suppression CLL.

Язык: Английский

Leukemic B cells expression of CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) in Chronic Lymphocytic Leukemia patients in relation to Tregs Frequency

Pathology - Research and Practice, Год журнала: 2024, Номер 263, С. 155669 - 155669

Опубликована: Окт. 21, 2024

Язык: Английский