公开(公告)号：US20220127572A1

公开(公告)日：2022-04-28

申请号：US17510902

申请日：2021-10-26

Applicant: UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO

Inventor： Maria Gloria SOLDEVILA MELGAREJO ,  Saul ARTEAGA CRUZ ,  Evelyn Katy ALVAREZ SALAZAR ,  Arimelek CORTES HERNANDEZ ,  Josefina ALBERU GOMEZ

IPC: C12N5/0783 ,  A61K9/00 ,  A61K39/00 ,  A61P37/06 ,  C12N5/0784

Abstract: A methodology to obtain large numbers of allospecific human Tr1 lymphocytes in vitro differentiated with phenotype and suppressive function stability in presence of proinflammatory cytokines, by using donor tolerogenic dendritic cells (DC10) derived from donor monocytes and from a not related receptor (allogeneic) naîve T cells cocultures. The obtained cells with the present methodology are characterized by the expression of a Tr1 regulatory phenotype (CD4+, CD49b+, LAG-3+), being high IL-10 producers, and also they express additional co-inhibitory molecules as PD1, TIM-3, CD39, CTLA-4 y TIGIT. Moreover, the cellular product obtained by this methodology is able to maintain a stable phenotype and suppressive function in presence of proinflammatory cytokines (IL-1β, IL-6, IFN-γ y TNF-α). The numbers, purity, and stability of the Tr1 obtained by this methodology, make them great candidates for their use as therapeutic tools in transplantation.