Abstract
Introduction:
Intra-abdominal candidiasis (IAC) still has a high mortality rate despite prompt antifungal therapy due to immunosuppression. T cell exhaustion is an important manifestation of immunosuppression. This study aimed to explore the expression pattern of exhaustion-related molecules in patients with IAC and determine the possible association between dynamic trends and prognosis.
Methods:
Patients with IAC were enrolled, and non-IAC critically ill patients were included as controls. Peripheral blood mononuclear cells (PBMCs) were analysed by flow cytometry to determine the expression levels of T cell exhaustion-related markers. T cells isolated from PBMCs were stimulated by IL-2 in α-CD3/α-CD28 medium to compare intracellular cytokine production and proliferative capacity.
Results:
A total of 34 patients with IAC and 35 controls were enrolled in this study. Patients with IAC had a significant decrease in lymphocytes. CD4+ and CD8+ T cells from patients with IAC had a significantly higher level of immune checkpoint molecules, such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA4), and B and T lymphocyte attenuator (BTLA), and exhibited a consistently impaired cytokine-secreting function. Increased exhaustion-associated molecules and deteriorating dysfunction were detected in non-survivors, while survivors demonstrated the opposite tendency. Patients with impaired granzyme B (GZMB) production function who died from IAC over the course of the disease had higher levels of PD-1 expression in CD8+ T cells.
Conclusions:
T cells from patients with IAC displayed an immunosuppressive phenotype of T cell exhaustion. Sustaining exhaustion status and deteriorated dysfunction were associated with poor prognosis. Persistently increased PD-1 expression and impaired GZMB secretion in CD8+ T cells were linked to worse outcomes. Immunoadjuvants reversing T cell exhaustion have promising prospects in treating IAC and improving prognosis.