Depletion of T cells by type I interferon: differences between young and aged mice.
Type I IFN (IFN-I or IFN-alphabeta) plays an important role in the innate immune response against viral infection. Here we report that a potent inducer of IFN-alphabeta, polyinosinic-polycytidylic acid [poly(I:C)], led to the depletion of T cells in young, but not aged mice, and that this depletion was limited to central memory, but not effector memory, T cells. Although early activation of T cells in vivo by poly(I:C), as demonstrated by CD69, was not impaired with aging, the expression of active caspase-3 was higher in young compared with aged mice. This depletion of T cells and induction of active caspase-3 in young mice and of CD69 in both young and aged mice by poly(I:C) were blocked by anti-IFN-alphabeta Ab. Although poly(I:C) stimulated lower circulating levels of IFN-alphabeta in aged mice, administration of IFN-alphabeta after poly(I:C) did not induce depletion of T cells in aged mice. These results indicate that IFN-alphabeta plays a critical role in the depletion of T cells of young mice, and further suggest that the lower level of functional IFN-alphabeta and decreased induction of active caspase-3 in T cells of aged mice after poly(I:C) may be responsible for the increased resistance of T cells of aged mice to depletion.
Jiang
Jiu
J
Department of Microbiology and Immunology, Drexel University, Philadelphia, PA 19129, USA.
Gross
Diara
D
Nogusa
Shoko
S
Elbaum
Philip
P
Murasko
Donna M
DM
D000375:Aging / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007369:Interferon Inducers / Q000008:administration & dosage; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000008:administration & dosage; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis
D007369:Interferon Inducers; D007370:Interferon Type I; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D011070:Poly I-C