Sci. Aging Knowl. Environ., 10 December 2003
Cells in the elderly immune system remember old skirmishes but not recent ones
Key Words: FACS analysis TH1 TH2 IL-2
Senior citizens who continually misplace their glasses can still recall childhood episodes in vivid detail. The immune system's "memory" seems to age similarly, according to new work. The study shows that immunological memories etched early in life persist, but those established in old age fade. The findings could explain why vaccines often are ineffective in older folks.
CD4 T cells orchestrate the immune system's response to invaders by recruiting other cells to the fight (see "Immunity Challenge"). But before they can do battle, so-called naïve T cells must encounter a foreign antigen, a molecule from an interloper, which galvanizes them to divide rapidly and dispense molecules that spur other immune cells to specialize and attack. Eventually, most of the new T cells die, but a few become memory cells, which linger in the body, ready to ambush a returning pathogen. Previous work showed that naïve T cells falter in older animals. For example, immunologists Susan Swain and Laura Haynes of the Trudeau Institute in Saranac Lake, New York, found that naïve T cells from elderly mice divide less vigorously and exude fewer immune-stimulating molecules. The researchers wanted to find out whether memory cells from older animals also stumble.
They started by obliterating the immune systems of youthful mice. Then they removed naïve T cells from normal young mice, stimulated them to divide and specialize by exposing them to an antigen, and pumped them into the immune-lacking rodents. One month and 1 year later, the researchers isolated memory cells from the recipients and tested their response to the antigen. Cells from both groups split at the same rate and released identical amounts of immune-stimulating compounds. The scientists then repeated the experiment using naïve T cells from aged mice. The memory cells they isolated from youthful recipients released paltry amounts of immune signals and were loath to divide. In short, naïve cells from young mice produce memory cells that are vigorous even after a year in a mouse's body, but naïve cells from old rodents spawn dud memory cells. These results suggest that whether memory cells become "forgetful" depends not on the length of time since they first encountered the antigen but on their age when they specialized.
CD4 cells also stimulate antibody-making B cells. The researchers found that memory cells derived from young naïve cells induced higher antibody output than did memory cells descended from old naïve cells. Older cells' ineptitude at spurring antibody production might explain why vaccines sometimes don't elicit immunity in the elderly, says Swain.
"It's a very good paper" that raises questions about when to give vaccines and how to increase their effectiveness for older people, says Phyllis-Jean Linton, an immunologist at the Sidney Kimmel Cancer Center in San Diego, California. Immunologist Rita Effros of the University of California, Los Angeles, also praises the work. But she says that we need further research to determine whether old naïve T cells are inherently defective or whether something in their environment corrupts them. Probing this question might help researchers discover how to jog the memory of elderly immune cells.
--Mitch Leslie; suggested by Amir Sadighi Akha and Greg Liszt
December 10, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150