Loss of CD28 expression on CD8(+) T cells is induced by IL-2 receptor gamma chain signalling cytokines and type I IFN, and increases susceptibility to activation-induced apoptosis

Int Immunol. 2000 Jul;12(7):1005-13. doi: 10.1093/intimm/12.7.1005.


CD8(+)CD28(-) T cells are selectively expanded during viral infections, indicating their importance in anti-viral immune responses. Since little is known about the differentiation of CD8(+)CD28(-) cells, we investigated the generation, function and survival characteristics of this subset. In healthy individuals CD8(+)CD28(-) T cells contained more elevated levels of perforin and IFN-gamma than the CD8(+)CD28(+) subset, indicating that they can have an effector function. CD8(+)CD28(-) cells were selectively expanded when activated CD8(+)CD28(+) T cells were cultured in IL-2, IL-7 or IL-15. Moreover, the generation of CD8(+)CD28(-) cells was accelerated by type I IFN suggesting that these cytokines which are released during viral infections influence CD8(+) T cell differentiation. We did not observe re-expression of CD28 by CD8(+)CD28(-) T cells in any of the experiments performed. Activated T cells are susceptible to activation-induced cell death (AICD) if re-stimulated in the absence of co-stimuli. AICD was induced in both CD28(+) and CD28(-) subsets of activated T cells when stimulated with anti-CD3 antibody in the absence of co-stimuli but the magnitude of death was greater in the CD28(-) subset. While co-stimulation through LFA-1 (CD11a and CD18) significantly reduced AICD in the CD8(+)CD28(+) subset, death was not prevented in CD8(+)CD28(-) cells. These results suggest that CD8(+)CD28(-) T cells are more functionally differentiated than the CD8(+)CD28(+) subset and indicate they may represent a terminally differentiated effector population which is destined for clearance by apoptosis at the end of the immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • CD28 Antigens / analysis*
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Differentiation
  • Cell Survival
  • Humans
  • Interferon Type I / pharmacology*
  • Lymphocyte Activation*
  • Receptors, Interleukin-2 / physiology*


  • CD28 Antigens
  • Interferon Type I
  • Receptors, Interleukin-2