Author response: Self-recognition drives the preferential accumulation of promiscuous CD4+ T-cells in aged mice
Year: 2015
Type: peer-review
Abstract: The immune system's T cells help the body to recognize and destroy harmful pathogens, such as viruses and bacteria. T cells ‘remember’ immunity-inducing fragments, called antigens, from the pathogens they have encountered. This memory then allows the immune system to quickly fend off infections if those pathogens, or even related pathogens, invade again. Vaccines exploit the ability to form immunological memory by exposing the body to harmless forms of the pathogen, or even just particular antigens from it. This allows the T cells to learn how to identify the pathogen without any risk of illness. Vaccines have been extremely successful and have helped to virtually eliminate some diseases. However, for reasons that are unclear, the immune systems of older adults become less functional, so vaccines often lose their effectiveness. Paradoxically, as people age T cells become more likely to attack the body's cells, causing autoimmune diseases like arthritis. Understanding what happens to aging T cells to cause these immune changes may help scientists design vaccines that remain effective as people age. Little is known about what happens to a particular type of T cell—the CD4+ T cells—as people age, even though this population plays a critical role in providing other immune cells with detailed instructions on when and how to fight a pathogen. Now, Deshpande et al. show that CD4+ T cells undergo a remarkable set of changes in aging mice. Mice that are nearing the end of their natural lifespan have fewer CD4+ T cells than younger mice. However, those CD4+ T cells that remain are more likely than CD4+ T cells from younger mice to be able to recognize multiple antigens. This increase in the proportion of multitasking CD4+ T cells corresponds with an increased tendency of these cells to bind to the body's own cells. If similar changes occur in older people, this may help explain some age-related autoimmune diseases. Yet, the relationship between the increase in multitasking CD4+ T cells and the decrease in immune function with aging remains to be fully explored. The challenge for scientists now is to determine how these age-related changes in CD4+ T cells affect immune responses to vaccines or pathogens in older individuals. One implication of this work is that CD4+ T cell responses may be too robust and out of balance with other arms of the immune system. This could even lead to conditions such as autoimmunity. Alternatively, while there may be more CD4+ T cells that can multitask by recognizing multiple antigens, their ability to respond appropriately to infections or vaccinations may be diminished. What is clear from the work of Deshpande et al. is that the rules that have been defined for immunity in adults change with aging. The rules that govern immunity in the elderly must be more clearly defined to realize the goal of designing immunotherapies, such as vaccines, that provide protection throughout the lifespan.
Source: eLife
Institution: University of Arizona
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W2985807079