|TRegs (Red with green nuclei) in skin|
It’s a well-known, but poorly-understood, observation that the elderly are more susceptible to disease; their immune system isn’t as effective. Not only are older people (and animals) at more risk of disease like influenza, they are also at risk of having a reactivation of some of the many chronic infections we pick up during our lives. And, of course, cancer is more common as one ages, as well.
There are lots of reasons why this might be the case, and likely most of them are factors. A recent paper supports a new and exciting possibility, offering evidence that part of the reason is an overactive immune response: An increase in regulatory T cell activity and numbers is partially responsible for the dampened defense against pathogens.1
Regulatory T cells are a critical component of the immune response; immune responses to pathogens are by their nature destructive, and TRegs are an important way of limiting the destruction. People and animals lacking TRegs have terrible (and usually rapidly fatal) autoimmune disease.
The development and regulation of TRegs themselves is still not all that well understood, but it’s generally accepted that there are at least two sources of TRegs: “Central” TRegs, that develop in the thymus as purpose-built regulatory cells, and “peripheral” TRegs, that are converted T cells that were originally from other lineages, like ninjas converting to zen Buddhism. Perhaps somewhere along this process there’s a small imbalance that, eventually, tilts the balance toward a gradual slow accumulation of TRegs.
In any case, TRegs do seem to be relatively more abundant in older animals. However, it wasn’t clear whether these accumulated cells are actually functional — after all, it’s known that many of the immune lineages in older animals have reduced function, perhaps the TRegs are also less effective, and you need more of them for that reason.
Lages et al demonstrated that this is not the case — in fact, TRegs in old mice are if anything more effective than those from young mice, in terms of suppressing immune responses. Even more interestingly — and this may translate into the clinic at some point — these TRegs are a part of the problem; reducing TRegs reduced disease, in at least some diseases. They used a model of Leishmania infection2 which is more severe in old mice than in young. Depleting the number of TRegs in older mice, though, made them much more resistant to disease — probably as resistant as the young mice.3
This is probably not universal, but it’s an exciting possibility. Perhaps things like shingles (reactivation of latent varicella-zoster virus) are actually manifestations of overactive TRegs, rather than an underactive effector response. Since we are much better at destruction of a response than creating one, this offers a much easier handle for treatment. I look forward to seeing followup on this.
By the way, my wife instructs me that we will be going on vacation for the first half of August, so I likely won’t be updating this blog as regularly for a bit. I aten’t dead.
- Functional Regulatory T Cells Accumulate in Aged Hosts and Promote Chronic Infectious Disease Reactivation. Celine S. Lages, Isabelle Suffia, Paula A. Velilla, Bin Huang, Gregg Warshaw, David A. Hildeman, Yasmin Belkaid and Claire Chougnet. The Journal of Immunology, 2008, 181: 1835-1848.[↩]
- Leishmania is a trypanosome parasite, transmitted by sand flies, that causes a variety of unpleasant diseases in people, as well as other species.[↩]
- I don’t think there’s a direct comparison of young vs. old depleted of TRegs, which is why I say “probably”[↩]