Boosting the Body’s Defense: How Unlocking T-Cell Potential Could Transform Treatment for Chronic Infections

February 14, 2025
Roberto Tinoco

In the battle against persistent viruses like HIV and hepatitis, our immune system faces a major obstacle — T-cell exhaustion. Over time, these vital defenders lose their ability to eliminate threats, making chronic infections harder to control. A team of scientists from the UC Irvine Charlie Dunlop School of Biological Sciences, led by Associate Professor Roberto Tinoco, has uncovered a new strategy that could change the game for treatments targeting these infections. Their study, published in the Journal of Virology, explores how fine-tuning the immune system’s “braking mechanisms” can unleash its full potential.

Chronic infections place T cells under constant stress, causing them to wear down and lose function. Current treatments use immune checkpoint inhibitors (ICIs) to block PD-1, a protein that suppresses T cells. However, these therapies don’t work for everyone, with many patients developing resistance. Professor Tinoco’s research introduces a second player, PSGL-1, a newer immune checkpoint with complementary but distinct effects. By disabling both PD-1 and PSGL-1 in experimental models, the team made a key discovery: while PD-1 inhibition boosts the number of T cells, PSGL-1 inhibition enhances their virus-fighting capabilities.

However, this discovery comes with a tradeoff. When only PD-1 was blocked, T cells expanded in number but lacked the power to fight effectively. Conversely, targeting PSGL-1 improved T-cell function but reduced their overall survival. The team suggests that a carefully coordinated approach — perhaps starting with PD-1 inhibition to build cell numbers and following up with PSGL-1 inhibition to boost function — could overcome these limitations.

This breakthrough paves the way for developing dynamic treatments tailored to each patient’s needs, potentially increasing the effectiveness of immunotherapies for chronic infections and even cancer. With further exploration, this approach could help address the problem of treatment resistance by making immune responses more robust and sustainable.

Learn more about the Tinoco Lab.