Too old to help
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《实验药学杂志》
Old mice have reduced CD4+ T cell function but, according to new data from Haynes and colleagues (page 845), the elderly environment is not to blame. Newly generated T cells functioned normally in elderly mice, suggesting that strategies to boost T cell production might be an effective way to improve vaccine efficacy in the elderly.
CD4+ T cells accumulate functional defects as they age. (T cell image provided by Michael Dustin, New York University, NY, NY.)
Previous work by this group has shown that age-related defects in antibody production result from declining CD4+ T cell help, not from faulty B cells. By depleting the existing pool of CD4+ T cells and forcing the thymus to churn out a fresh supply, the authors show that newly generated CD4+ T cells are equally responsive to antigen whether they are produced in a young or an old mouse. This suggests that their functional demise depended on the age of the individual T cell, not on the age of the mouse.
Although there were no detectable phenotypic differences between old and young T cells, the authors postulate that unknown defects accumulate in T cells as they divide and age in the periphery. In young mice, the new T cells produced by the thymus compensate for the reduced function of their elderly predecessors. But thymic output decreases with age, and eventually old T cells outnumber young ones, causing overall T cell function to decline. Production of B cells, by contrast, does not decrease as drastically with age, which may explain why B cells are more resistant to the effects of aging.
Although the nature of the defects that accumulate in aging T cells are not known, recent studies showing an age-related decrease in immune synapse formation between T cells and antigen presenting cells point to potential alterations in plasma membrane components. Haynes suggests that changes in the lipid composition of the plasma membrane—possibly resulting from routine oxidative stress—may make the membranes less fluid and slow down the movement of key signaling molecules into the immune synapse.(Heather L. Van Epps)
CD4+ T cells accumulate functional defects as they age. (T cell image provided by Michael Dustin, New York University, NY, NY.)
Previous work by this group has shown that age-related defects in antibody production result from declining CD4+ T cell help, not from faulty B cells. By depleting the existing pool of CD4+ T cells and forcing the thymus to churn out a fresh supply, the authors show that newly generated CD4+ T cells are equally responsive to antigen whether they are produced in a young or an old mouse. This suggests that their functional demise depended on the age of the individual T cell, not on the age of the mouse.
Although there were no detectable phenotypic differences between old and young T cells, the authors postulate that unknown defects accumulate in T cells as they divide and age in the periphery. In young mice, the new T cells produced by the thymus compensate for the reduced function of their elderly predecessors. But thymic output decreases with age, and eventually old T cells outnumber young ones, causing overall T cell function to decline. Production of B cells, by contrast, does not decrease as drastically with age, which may explain why B cells are more resistant to the effects of aging.
Although the nature of the defects that accumulate in aging T cells are not known, recent studies showing an age-related decrease in immune synapse formation between T cells and antigen presenting cells point to potential alterations in plasma membrane components. Haynes suggests that changes in the lipid composition of the plasma membrane—possibly resulting from routine oxidative stress—may make the membranes less fluid and slow down the movement of key signaling molecules into the immune synapse.(Heather L. Van Epps)