Prognostic Value and Potential Mechanism of CD8+ T Subsets Phenotype in ICU Patients with Sepsis

Background: While CD8 + T-cell subsets play a crucial role in sepsis prognosis, the prognostic value of their dynamic changes and molecular mechanisms remains incompletely understood. Compared to static single-timepoint measurements, the prognostic role of repeated measurements over time remains undetermined. Methods: The study included 220 intensive care unit patients with sepsis (2023.08–2024.05). K-means clustering analysis based on CD8 + CD28 + /CD8 + %, CD8 + CD38 + /CD8 + %, and CD8 + DR + /CD8 + % was used to categorize patients into two groups. Clinical data were collected and analyzed for 28-day mortality prediction. Fifteen patients from each group were selected for Olink proteomics analysis to investigate differentially expressed proteins and conduct functional enrichment analysis. Results: Using K-means clustering analysis based on CD8 + T-cell subset phenotypes, patients were divided into group 1 (n = 74) and group 2 (n = 146), with group 2 demonstrating significantly higher 28-day mortality compared to group 1 (32.3% vs. 17.6%, P < 0.001). Further dynamic trend analysis revealed that patients exhibiting continuously decreasing CD8 + CD28 + /CD8 + % and increasing CD8 + CD38 + /CD8 + % had the poorest prognosis, with a 28-day mortality rate of 50%. The combined measurement of CD8 + CD28 + /CD8 + % and CD8 + CD38 + /CD8 + % showed enhanced prognostic value (area under the curve = 0.676) compared to individual measurements, indicating the importance of monitoring multiple T-cell subset markers. Additionally, Olink proteomic analysis identified IL-12Rβ1 as a key molecular mediator closely associated with CD8 + T-cell function and activation subsets, providing insights into the underlying mechanism of immune dysfunction in sepsis patients. Conclusions: CD8 + T-cell subset phenotypes serve as important prognostic indicators in sepsis, with IL-12Rβ1 potentially being a key molecule affecting CD8 + T-cell function, providing a new potential target for sepsis monitoring and immunotherapy.