T Cell Differentiation And Function In Tissue Inflammation PDF Download

Upon antigen encounter, naïve T cells differentiate into (i) effectors that combat infected or malignant cells, and at later time points, into (ii) memory cells that provide long-lasting immunity. This differentiation process allows some T cells to leave the confines of secondary lymphoid organs and to enter peripheral tissues in search of pathogens or tumor cells. These different environments pose specific challenges for effector and memory T cells to maintain homeostasis. T cells directed into the lungs are likely to encounter higher levels of oxygen, but lower amounts of nutrients than those directed into the intestinal epithelium. In addition to oxygen tension and nutrient concentrations, other key factors, such as the commensal flora and stromal components, create unique conditions that require tissue-specific adaptations of T cells. These steady state conditions can dramatically change during infection when inflammatory mediators and T cell growth factors are released, requiring the immediate response of T cells. The gradual changes imposed by growing tumors can also be challenging for T cells due to competition with rapidly cycling tumor cells that deplete essential resources of oxygen and glucose. The strategies that T cells employ to respond to the diverse cues from their surroundings are the focus of current research. It appears that next to circulating memory T cells that are confined to the circulation and those that survey all of the peripheral tissues, dedicated populations of resident memory T cells exist that can optimally adapt to the local circumstances within each tissue. Restrictions on the metabolic requirements of T cells residing in tumor tissue have been found to directly impact on effector functions such as cytokine production. The fundamental principles of how the machinery of T cells can translate local cues into tissue-specific differentiation processes are fascinating and warrant further investigation.