T Cell Tunnel Vision

Abstract

Like a chef who's so engrossed in making the spaghetti sauce that she burns the garlic bread, the aged immune system seems to concentrate its efforts. Scientists don't know what causes this focus, but new research reveals that a common virus captures the system's attention in elderly people. The results raise the possibility that prevalent pathogens might narrow the immune system's capacity, perhaps diminishing the body's ability to respond to new germs. Immune system soldiers called CD8 T cells identify foreign agents. Each cell wields a single type of receptor molecule on its surface that grabs a particular pathogen snippet--an antigen--on an infected cell. If the antigen fits, the CD8 cell multiplies, creating a battalion of clones poised to destroy host cells infected with the antigen-bearing agent. In youthful immune systems, thousands of unique CD8 cell regiments recognize a pathogen's many different antigens and together annihilate it. In older people and mice, a small number of CD8 cells reproduce too much, creating an army with only a few plans of attack. Researchers can determine how many progenitor cells cloned themselves, but is has been a mystery which antigens they bind and why some clones overtake the CD8 cell population. Although some scientists think that the clones are innocuous, others speculate that filling space with these T cells reduces the immune system's ability to combat new infections. In previous research, Khan and colleagues noticed that, compared with 20-somethings, older subjects mounted a greater response against cytomegalovirus (CMV), a relatively harmless virus that hides out in most healthy adults. The team members decided to test whether the latent virus might spur overproduction of CD8 clones in the elderly. First, the researchers took blood samples from two groups of volunteers with an average age of 73 or 31. The older individuals dedicated four times as many of their CD8 soldiers to a single CMV antigen as the younger subjects did. Infected seniors also had a third more overpopulated clone battalions--not all of which targeted CMV--than did uninfected individuals in the same age group. Additional biochemical analysis revealed that the CMV antigen-binding cells from infected individuals descended from one or two CD8 cells in each person. The data suggest that CMV infection can provoke proliferation of particular CD8 cells. Whether this propagation interferes with immune function is still unclear. The "key question," according to biogerontologist Richard Miller of the University of Michigan, Ann Arbor, is whether other viruses have the same effect. Because CMV didn't account for all the elderly people's CD8 cell clones, he wants to know, "What is their source besides CMV?" Immunologist Philippa Marrack of the University of Colorado Health Sciences Center in Denver says that the work might help scientists figure out why certain CD8 cells tend to overproduce. If such proliferation distracts the immune system from its many responsibilities, helping it multitask could preserve its versatility into old age, much as prodding the cook to check the oven might save the bread from scorching. --Mary Beckman; suggested by Jennifer Fuller and Amir Sadighi Akha N. Khan, N. Shariff, M. Cobbold, R. Bruton, J. A. Ainsworth, A. J. Sinclair, L. Nayak, P. A. H. Moss, Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J. Immunol. 169 , 1984-1992 (2002). [Abstract] [Full text]