Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory

Academic Article

Abstract

  • Although the role of CD28-B7 interaction in the activation of naive T cells is well established, its importance in the generation and maintenance of T cell memory is not well understood. In this study, we examined the requirement for CD28-B7 interactions in primary T cell activation and immune memory. Ag-specific CD8 T cell responses were compared between wild-type (+/+) and CD28-deficient (CD28-/-) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During the primary response, there was a substantial activation and expansion of LCMV-specific CD8 T cells in both +/+ and CD28-/- mice. However, the magnitude of the primary CD8 T cell response to both dominant and subdominant LCMV CTL epitopes was ∼2-to 3-fold lower in CD28-/- mice compared with +/+ mice; the lack of CD28-mediated costimulation did not lead to preferential suppression of CD8 T cell responses to the weaker subdominant epitopes. As seen in CD28-/- mice, blockade of B7-mediated costimulation by CTLA4-Ig treatment of +/+ mice also resulted in a 2-fold reduction in the anti-LCMV CD8 T cell responses. Loss of CD28/B7 interactions did not significantly affect the generation and maintenance of CD8 T cell memory; the magnitude of CD8 T cell memory was ∼2-fold lower in CD28-/- mice as compared with +/+ mice. Further, in CD28-/-mice, LCMV-specific memory CD8 T cells showed normal homeostatic proliferation in vivo and also conferred protective immunity. Therefore, CD28 signaling is not necessary for the proliferative renewal and maintenance of memory CD8 T cells.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Suresh M; Whitmire JK; Harrington LE; Larsen CP; Pearson TC; Altman JD; Ahmed R
  • Start Page

  • 5565
  • End Page

  • 5573
  • Volume

  • 167
  • Issue

  • 10