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The Journal of Immunology, 2002, 168: 3777-3785.
Copyright © 2002 by The American Association of Immunologists

Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection1

Edward M. Bertram, Peggy Lau and Tania H. Watts2

Department of Immunology, University of Toronto, Toronto, Ontario, Canada

In this report, we demonstrate that CD28-/- mice are severely impaired in the initial expansion of Db/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)-/- mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL-/- mice show a decrease in Db/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL-/- mice show a decrease in the number of Db/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.




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