Donor-specific immune regulation by CD8+ lymphocytes expanded from rejecting human cardiac allografts
To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic-stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T-cell response of PBMC, but not the anti-third-party response. Interestingly, it was the CD8+GL subset of these cultures that inhibited the antidonor response (65-91% inhibition of the proportion of proliferating cells); the CD4+GLs of the expanded GL cultures were not suppressive. In conclusion, CD8+GLs expanded from rejecting human cardiac allografts can exhibit donor-specific immune regulatory activities in vitro. We suggest that during acute cellular rejection, GLs may not only consist of graft-destructing effector T cells, but also of cells of the CD8+type with the potential to specifically inhibit antidonor immune reactivity.
|Keywords||Acute cellular rejection, Antigen-specificity, Endomyocardial biopsy, Graft-infiltrating lymphocytes, Heart transplantation, Human, Immune regulation|
|Persistent URL||dx.doi.org/10.1111/j.1600-6143.2008.02498.x, hdl.handle.net/1765/24859|
Dijke, I.E., Caliskan, K., Klepper, M., de Kuiper, R., Balk, A.H.M.M., Maat, A.W.P.M., … Baan, C.C.. (2009). Donor-specific immune regulation by CD8+ lymphocytes expanded from rejecting human cardiac allografts. American Journal of Transplantation, 9(2), 397–403. doi:10.1111/j.1600-6143.2008.02498.x