Association Between Programed Cell Death-1 and CD4+ T Cell Alterations in Different Phases of Ischemic Stroke Patients

Objective: We aimed to analyze alterations in T cell subgroups during different post-ischemic stroke (IS) phases to explore the possible mechanisms underlying stroke-induced immune depression (SIID).

Methods: Sixty-four IS patients who met the entry criteria were divided into three groups: an acute phase group, a sub-acute phase group and a stable phase group. Fourteen healthy individuals were selected as normal controls. The phenotype distribution of T cells in patient peripheral blood was analyzed, and the immune checkpoint receptors programed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) were detected in different T cell phenotypes.

Results: Compared with the control group, the absolute number of CD4+ T cells and CD4+ T central memory (TCM) cells was significantly increased in the acute phase group but decreased in the sub-acute phase and stable phase groups compared with that in the acute phase group. PD-1 expression in CD4+ T cells in the stable phase group showed a significant increase compared with that in the acute phase group. The expression of PD-1 on CD4+ TCM cells and CD4+ T effector memory (TEM) cells showed significant decreases in the acute phase compared with control cells; however, in the sub-acute phase and the stable phase, PD-1 expression was significantly increased compared with that in the acute phase.

Conclusions: T cell dysfunction, especially CD4+ T cell dysfunction, occurred during different IS phases. PD-1 was highly expressed in CD4+ T cells of different phenotypes after the acute phase and was associated with alterations in CD4+ T cells. Particularly, PD-1 was negatively correlated with the absolute number of TCM cells among different CD4+ T cell phenotypes, which may be one of the possible mechanisms of SIID.