Tuberculosis: TB is a major cause of global morbidity and mortality, killing up to 1.5 million people every year. Despite tremendous progress in our understanding of TB, infections are increasing, multidrug resistant bacterial strains are on the rise, and impoverished people with little access to long, expensive treatments continue to bear the brunt of disease. The only existing vaccine against TB was developed more than 90 years ago and is largely ineffective in certain populations and against pulmonary TB. The largest barrier to development of an effective TB vaccine is our failure to understand the fundamental characteristics of a protective immune response.
CD4 T cells are essential for host protection, and recent data suggests that CD4 T cells homing to the lung parenchyma participate in this response. The non-circulating status of these T resident memory (TRM) cells allows them to rapidly respond at the site of antigen exposure, making them an attractive therapeutic target for vaccination. Very little is currently known about the cellular regulation or transcriptional programs leading to CD4 TRM generation, survival and function. We hypothesize that CD4 TRM cells play diverse protective roles and persist interdependently within specific lung niches.
CD4 T cells are essential for host protection, and recent data suggests that CD4 T cells homing to the lung parenchyma participate in this response. The non-circulating status of these T resident memory (TRM) cells allows them to rapidly respond at the site of antigen exposure, making them an attractive therapeutic target for vaccination. Very little is currently known about the cellular regulation or transcriptional programs leading to CD4 TRM generation, survival and function. We hypothesize that CD4 TRM cells play diverse protective roles and persist interdependently within specific lung niches.