Cutting Edge: T Cells from Aged Mice Are Resistant to Depletion Early During Virus Infection

Abstract

Aging is associated with decreased expansion of T cells upon stimulation. In young mice, infection induces a transient T cell depletion followed by the development of an Ag-specific T cell response that controls the infection. We found that T cells were depleted early after infection with E55 + murine leukemia retrovirus in young, but not aged, mice. Adoptive transfer experiments showed donor T cells of young, but not aged, mice were depleted due to apoptosis in various tissues of young recipients. However, T cells of neither young nor aged donors were depleted in aged recipients. These results indicate that both environmental and intrinsic cellular properties limit depletion of T cells of aged mice and suggest a novel explanation for the decreased T cell response associated with aging.

Depletion of T Cells by Type I Interferon: Differences between Young and Aged Mice

“…2) Is there up-regulation of markers associated with apoptosis after poly(I:C) administration? Comparable to our previous data with E55ϩMuLV (9), the number of both CD4 and CD8 T cells did not increase, but decreased although not significantly in mesenteric lymph nodes and blood 24 h after inoculation of poly(I:C) in young mice (Fig. 2).…”

“…Our previous results have shown that the depletion of T cells in young mice early during viral and bacterial infections is due to apoptosis (7,9). To examine whether the depletion of T cells in young mice after stimulation with poly(I:C) is related to apoptosis, we examined two questions: 1) Is comparable depletion seen in other tissues, therefore eliminating the possibility that the decreased numbers in the spleen reflects migration rather than apoptosis?…”

“…In our previous studies, we reported that CD8 and CD4 T cells of young, but not aged, mice were depleted by apoptosis during the early stage of virus infection (9). To investigate whether IFN-␣␤ is involved in T cell depletion in young and aged mice, we used a strong inducer of IFN-␣␤, poly(I:C), which is considered an agent that mimics virus infection (24).…”

“…Based on this information, we previously performed studies that demonstrated early after E55ϩmurine leukemia virus (E55ϩMuLV) 3 infection there is a nonspecific depletion of both naive and memory T cells in young mice that occurs via apoptosis (9). This depletion does not occur in aged mice after virus infection (9). We hypothesize that this lack of "space" in the lymphocytic compartment may be responsible for the decreased specific T cell response of aged mice to virus infections.…”

“…They postulated that this depletion of nonresponding T cells may be necessary for the subsequent proliferation and expansion of specific T cells required for clearance of the infectious agents. Based on this information, we previously performed studies that demonstrated early after E55ϩmurine leukemia virus (E55ϩMuLV) 3 infection there is a nonspecific depletion of both naive and memory T cells in young mice that occurs via apoptosis (9). This depletion does not occur in aged mice after virus infection (9).…”