profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells.

For those curious what this means:

• 1. Impaired T Cell Activation: CD4+ T cells, also known as helper T cells, are crucial for initiating and coordinating the immune response. CD8+ T cells, or cytotoxic T cells, are responsible for directly killing infected or cancerous cells. If the activation of these cells is impaired, the immune system's ability to recognize and respond to pathogens, cancer cells, or other threats is weakened. This can result in a diminished ability to clear infections or control tumor growth.
• 2. Increased PD-1 Expression: PD-1 (Programmed Cell Death Protein 1) is an inhibitory receptor found on the surface of T cells. When PD-1 binds to its ligands (PD-L1 or PD-L2), it sends a signal that reduces T cell activity, leading to "exhaustion" of T cells. This is a mechanism often exploited by cancer cells to evade the immune system. Increased PD-1 expression on T cells would therefore further inhibit their function, leading to reduced immune surveillance and a weakened response against tumors or chronic infections.
• 3. Increased LAG-3 Expression: LAG-3 (Lymphocyte-activation gene 3) is another inhibitory receptor that functions similarly to PD-1. It negatively regulates T cell activation and proliferation. Increased expression of LAG-3 would compound the effects of PD-1, further dampening T cell responses.

• Overall Impact: The combination of impaired T cell activation and increased inhibitory signals (via PD-1 and LAG-3) would lead to a state of immune exhaustion. This would result in a reduced ability to fight infections, a higher likelihood of chronic infections persisting, and an increased risk of cancer cells evading immune detection and growing unchecked.