GammaDelta · DECIPHERING THE MEMORY OF gd T CELLS: DOES IT HAVE A ROLE IN CROSS-PROTECTION OF BACILLE CALMETTE-GUERIN VACCINATION?

DECIPHERING THE MEMORY OF gd T CELLS: DOES IT HAVE A ROLE IN CROSS-PROTECTION OF BACILLE CALMETTE-GUERIN VACCINATION?

Recent events of SARS-Cov2 pandemic, which has claimed life of over 500 000 people worldwide within only half a year (according to Johns Hopkins Coronavirus Resource Center) and is still accelerating, have shown how threatening the infectious diseases can be in the era of globalization and how important it is to develop effective vaccination strategies. The efficacy of vaccines relies on the ability of immune cells to “memorize” previous invaders and in consequence to respond more efficiently to the secondary exposure to the pathogen. This phenomenon is called immunological memory. While vaccines are designed to protect against a specific pathogen, it has been shown that some of them have a cross-protective effect, meaning that they can protect against non-targeted infections. One example of a vaccine with known heterologous effects is bacillus Calmette-Guerin (BCG) vaccine developed to protect against tuberculosis caused by Mycobacterium tuberculosis. Based on its potency to enhance immune responses towards various pathogens and the urgency to combat SARS-Cov2 pandemic, clinical trials are currently ongoing to evaluate its protective effects against SARS-Cov2 infection. The molecular basis of cross-protective effect can be explained by, among others, “trained immunity”. Trained immunity is the ability of innate immune cells (such as macrophages or natural killer cells) to “remember” primary stimulations (for example by BCG) and to respond more effectively to the secondary challenge, thus generating memory-like immune responses. While the immune memory has been for decades attributed solely to the adaptive immune cells (B and T cells) and is known to be antigen-specific, trained immunity has been described recently and is not antigen-specific. Therefore it can be cross-protective. It has been established that cells of the adaptive immune system develop immunological memory and some cells of the innate immune system develop trained immunity. Yet, it remains to be determined what kind of immune memory: adaptive or innate-like characterizes immune cells which share features of both: adaptive and innate immune cells and what is their contribution to immune memory responses? This project aimed to assess the memory character of innate-like T cells, called gamma delta (gd) T cells, and its contribution to the immune memory responses upon BCG vaccination. gd T cells are classified as adaptive immune cells based on the expression of T cell receptor (TCR), similarly to conventional alpha beta (ab) T cells. However their immune responses are of innate character: not pathogen-specific and fast. BCG vaccination has been shown to generate memory gd T cells however their memory character was only assessed in a pathogen-specific context. In this study we examined the gd T cell immune responses to heterologous stimuli and show that despite the innate character, gd T cells do not develop trained immunity therefore they can only account for pathogen-specific memory responses.

Data: CORDIS, © European Union