ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition.

The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-µM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.

Study on preparation of a Streptococcus suis ghost vaccine.

Streptococcus suis (S.suis)is an important zoonotic pathogen in pigs and human. Bacterial ghosts (BGs) which are empty envelopes were used recently as efficient delivery system in vaccine development. In this study, S.suis ghosts were prepared and protective efficacy was evaluated in mice. Sodium hydroxide was used to prepare S.suis ghosts which were visualized under scanning electron microscopy. The optimum concentration of is Sodium hydroxide 6 mg/mL for ghosts formed. To investigate the S.suis ghosts as a candidate vaccine, the 50 BALB/c mice were randomly divided into three groups: Group A (control group), group B (subcutaneous injection of inactivated S.suis 2), group C (subcutaneous injection of inactivated S.suis 9), group D (subcutaneous injection of S.suis 2 ghosts), group E (subcutaneous injection of S.suis 9 ghosts). Serum were collected from five groups on the day of 7, 14, 21 and 28 after the first immunization for potency assay. Indirect ELISA results showed that antibody titer of blood serum of mice from group S.suis2 ghosts and group S.suis9 ghosts were significantly higher than blank group(P < 0.01), but were approximate to the conventional inactivated vaccine group SS2. In comparison with the conventional inactivated vaccine, S.suis ghosts as candidate vaccine strategy showed the excellent immunogenicity and provided protection against S.suis challenge in mice model.