Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.

ABSTRACT: The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity. We characterized T cell responses by flow cytometry and identified an exhausted-like population of CD2low CD4 effector memory T cells coexpressing TIGIT and PD1 that expanded by 11 wk after the start of treatment. This population was not entirely spared from alefacept-mediated depletion in vivo or in vitro but recovered through home

SUBMITTER: Higdon LE 

PROVIDER: S-EPMC11844141 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature