A subset of CD8+ T cells acquiring selective suppressive properties may play a role in GvHD management

Difficulty in segregating graft-versus-tumor effect (GvT) from graft-versus-host disease (GvHD) remains a major limitation of allogeneic stem cell transplantation (Allo SCT). Naturally occurring regulatory T cells have been suggested to suppress alloreactive T cells involved in GvHD; however, their non-selective suppressive effect raises concern regarding probable attenuation of the GvT effect. Recent studies suggested inducible CD8 (iCD8) cells to be useful in suppressing autoimmune reactions, although their function in the Allo SCT setting has not been fully explored. The current study assessed in-vitro the properties of iCD8 T cells, generated in response to allogeneic dendritic cells (DCs), imitating the Allo SCT conditions. CD25− peripheral blood mononuclear cells (PBMCs) were stimulated with allogeneic DCs in mixed lymphocyte culture (MLC). The resultant iCD8+CD25+ population was isolated and assessed for phenotypic markers, cytokine expression profile, cell proliferation, inhibitory capacity and anti-viral response. The generated CD8+CD25+FOXP3+ T cells selectively inhibited the primary allogeneic response, without attenuating T cell response against other stimuli, such as mitogens or a cytomegalovirus (CMV) recall antigen. In conclusion, iCD8+CD25+ cells suppress allogeneic stimulation, while maintaining the capacity to respond to infectious pathogens. These cells could be potentially efficient in the Allo SCT setting, where GvHD prevention is required.

► Assessment of inducible CD8 generated in response to allogeneic dendritic cells ► Inducible CD8+ T cells exhibit regulatory markers: CD25, FOXP3, GITR and CTLA-4. ► Induced CD8+ cells inhibit response to primary allogeneic but not to other stimuli. ► Induced CD8+ cells exhibit inflammatory cytokines: IL-2 and IFN-γ. ► CMV sero-positive induced CD8+ cells respond to stimulation with CMV protein.