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.
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.
Borthwick
N J
NJ
Departments of Clinical Immunology, Royal Free and University College Hospital Medical Schools, London NW3 2PF, UK.
Lowdell
M
M
Salmon
M
M
Akbar
A N
AN
D017209:Apoptosis; D018106:CD28 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002470:Cell Survival; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000502:physiology*
D018106:CD28 Antigens; D007370:Interferon Type I; D015375:Receptors, Interleukin-2