Increased apoptosis of CD45RO- T cells with aging.

Increasing susceptibility to infectious and autoimmune phenomena have long been recognized to accompany advancing age in otherwise healthy individuals. Recently animal models of aging have suggested that age-associated immune dysfunction may correlate with defects in T cell apoptosis. We have examined activation-induced apoptosis defects in human peripheral T cells from young individuals (mean age = 31 +/- 3 years old) compared to aged individuals (mean age = 67 +/- 8 years old). Following in vitro activation of T cells with PHA and IL-2, apoptosis was measured in T cell subsets using 7-amino actinomycin D (7-AAD) staining and analysis via three colour flow cytometry. There was no significant difference in apoptosis of the total CD3+ T cell population at early and late time points. Interestingly, increased apoptosis in the CD3+ CD45RO- T cell population of older adults was observed by culture day 6. While the total number of CD3+ CD45RO- cells was not different between young (< 33 years) and old (> 65 years) individuals, 32% of these cells did not undergo apoptosis in younger individuals while only 10% of these cells avoided this fate in older individuals. These results suggest that accumulation of CD45RO+ T cells may occur in aged subjects due in part to preferential elimination of CD45RO- cells with activation. Furthermore, as new or continued immune response requires differentiation of CD45RO+ T cells to CD45RO+ T cells after activation, increased apoptosis instead of survival in aged individuals could lead to observed T cell immune deficiency.

Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection.

Mechanisms of parasite killing by eosinophils are widely studied and are often implicated in mediating resistance to parasitic infection, especially in conjunction with specific antibodies. Evidence for the eosinophil as an anti-parasite killer cell in vivo is limited and may not justify the belief that eosinophils engage and/or kill infective helminths. We reexamined this question in a mouse model of trichinosis in which antisera to eosinophils were previously used to show the requirement for eosinophils in resistance to this nematode. The current studies used mAb to IL-5 to suppress eosinophil levels in CF1 mice infected with Trichinella spiralis. In mice given a primary infection and injected with an isotype control mAb or left untreated, the medullary and peripheral blood eosinophil numbers peaked at 3 wk postinfection (PI) and returned to baseline levels by 4 wk PI. Peripheral blood eosinophil numbers in infected mice injected with anti-IL-5 were maintained at levels below those of uninfected normal mice through 4 wk of infection. Histologically, there was a prominent eosinophil accumulation in infected, untreated, or control-mAb-treated mice associated with nurse cell complexes containing infective juveniles in skeletal muscle at 3 and 4 wk PI. This was largely eliminated in mice treated with anti-IL-5 mAb. However, the number of muscle stage juvenile worms recovered 3 and 4 wk PI after acid pepsin digestion was unaffected by eosinophil depletion. Challenge infections, in which mice were infected at day 0 with 125 muscle stage worms and challenged at day 28 PI with 350 muscle stage worms, developed peak eosinophil numbers in bone marrow and peripheral blood 3 wk after primary infection and 2 wk after challenge infection in mice receiving either no treatment or control mAb. In challenged mice receiving anti-IL-5 mAb, medullary and peripheral blood eosinophil numbers remained at or below those of uninfected animals. Although all groups exhibited significant resistance measured as muscle stage worm burdens 56 days PI, eosinophil depletion did not affect resistance of muscle worm recovery. These results suggest that eosinophils are not essential in the control of T. spiralis in either primary or challenge infections of CF1 mice. This in vivo study illustrates the questionable value of in vitro killing assays to assign effector function to any single inflammatory cell type.