Arguing that Cytomegalovirus is Beneficial for Old Immune Systems

Researchers here make the intriguing argument that persistent cytomegalovirus (CMV) infection results in a better rather than worse immune system in old age, for at least some measures. This stands in opposition to the current consensus and broad range of evidence to show that much of the disarray of the aged immune system is due to CMV and similar latent viral infections. Too large a portion of the limited resources of the adaptive immune system becomes devoted to these foes, at a point in life when new T cells are created slowly, if at all. The thymus, where T cells mature, atrophies in later life, while the hematopoietic stem cell pool responsible for creating immune cells declines in function.

A number of potential immunotherapies work by provoking the immune system into greater activity; these are largely blunt tools, and can have serious side-effects. The argument in here is a similar one, perhaps, that the presence of CMV is provoking the immune system, thus making the immune response more effective in some ways than might otherwise have been the case. A caution here is that mouse and human adaptive immune systems are quite different in their dynamics in late life, and this may well be an important difference in this context. In old humans very few new T cells arrive from the thymus, and most are produced from replication in existing populations. In old mice, a much larger fraction of T cells emerge from the thymus. If the effects of CMV involve both firing up the immune system and causing too many cells to be specialized to attacking CMV rather than other tasks, then this could balance out to be a net benefit in mice and a net harm in humans.

Our immune system is at its peak when we’re young, but after a certain age, it declines and it becomes more difficult for our bodies to fight off new infections. In search of a way to rejuvenate the immune system of older adults, scientists began researching cytomegalovirus, or CMV. The virus, which is usually contracted at a young age, affects more than half of all individuals. Because there is no cure, the virus is carried for life and is particularly prevalent in older adults. “CMV doesn’t usually cause outward symptoms, but we still have to live with it every day since there’s no cure. Our immune system always will be busy in the background dealing with this virus.”

Researchers wondered how this lifelong virus ultimately affects the immune system. To study the effects of CVM, they infected mice with the virus. “We assumed it would make mice more vulnerable to other infections because it was using up resources and keeping the immune system busy. But that’s not what happened. When infected with listeria, old mice carrying CMV proved to be tougher than old mice without CMV. We were completely surprised; we expected these mice to be worse off. But they had a more robust, effective response to the infection.” Researchers are not certain how CMV strengthens the immune system – they are investigating that in a separate study – but they do believe they have gained new insight into the aging immune system.

For years, immunobiologists thought T-cells – the army of defenders that fights off infection – decreased in diversity as people aged, leaving older adults more susceptible to diseases. But when researchers examined the mice’s T-cells, they found both groups of older mice had a decent supply of diverse T-cells. “Diversity is good. Different types of T-cells respond to different types of infections; the more diverse T-cells you have, the more likely you’ll be able to fight off infections.” The study shows that T-cells are almost as diverse in old mice as they are in young mice. The problem is diverse T-cells are not recruited to the battlefield in older mice unless they are infected with CMV. “It’s as if CMV is issuing a signal that gets the best defenses out onto the field. This shows that the ability to generate a good immune response exists in old age – and CMV, or the body’s response to CMV, can help harness that ability.”


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