Defective T cell priming associated with aging can be rescued by signaling through 4-1BB (CD137)

P Bansal-Pakala, M Croft - The Journal of Immunology, 2002 - journals.aai.org
P Bansal-Pakala, M Croft
The Journal of Immunology, 2002journals.aai.org
Aging is associated with an increased susceptibility to infectious agents and correlates with
a decreased ability to mount an immune response. It has been postulated that the major
defect is related to a reduced capacity of an aged T cell to proliferate and to survive after
encounter with Ag. This is similar to the phenotype associated with T cell tolerance in young
adults. In this study, we determined whether targeting 4-1BB (CD137), a member of the
TNFR family implicated in providing expansion and survival signals to T cells, can rescue …
Abstract
Aging is associated with an increased susceptibility to infectious agents and correlates with a decreased ability to mount an immune response. It has been postulated that the major defect is related to a reduced capacity of an aged T cell to proliferate and to survive after encounter with Ag. This is similar to the phenotype associated with T cell tolerance in young adults. In this study, we determined whether targeting 4-1BB (CD137), a member of the TNFR family implicated in providing expansion and survival signals to T cells, can rescue defective priming in aged and tolerized animals. Agonist Abs to 4-1BB injected in vivo were capable of preventing CD4 T cell tolerance to soluble peptide in young mice. Moreover, anti-4-1BB rescued defective priming of aged TCR transgenic CD4 T cells responding to peptide Ag in a young host, and as importantly, anti-4-1BB completely restored T cell priming to protein Ag in nontransgenic aged mice. These studies demonstrate that 4-1BB, and potentially other costimulatory members of the TNFR family, are targets for therapies aimed at augmenting weak T cell responses in elderly immunocompromised individuals.
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