Survival following lung transplantation is less than 50% at 5 years following transplantation, mainly due to chronic allograft rejection. Combating chronic rejection is the key to improved survival. Recently a novel subset of T cells, CD4-veCD8-ve CD30+ve, so-called double negative (DN) CD30+ve T cells, has been described and shown to be responsible for tolerance in an animal model of skin transplantation. Our aim is to document the presence/absence of DN CD30+ T cells in lung transplant recipients.
Using flow cytometry we measured DN CD30+ve T cells in resting peripheral blood of lung transplant recipients and following in vitro stimulation of recipient peripheral blood mononuclear cells (PBMCs) with donor spleen cells. We checked for correlation between CD30 expression and clinical course following lung transplantation.
Small percentages (<2%) of DN T cells are detectable in resting peripheral blood of human transplant patients (N=18) but did not correlate with allograft function, acute rejection episodes, HLA mismatch, or CMV status. On repeated stimulation of recipient PBMCs (2 exposures) in vitro by donor spleen cells (2:1 ratio stimulators to responders) the percentage of DN CD30+ve T cells correlated with preservation of allograft lung function (both for FEV1, p=0.009, and FEF25–75, p=0.036, N=18) and was inversely correlated with grade of chronic rejection. The total number of HLA mismatches correlated with the percentage DN CD30+ve T cells present after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio). The number of mismatches at the HLA B locus inversely correlated with the percentage of DN CD30+ve T cells after primary stimulation of recipient PBMC with donor spleen cells (1:1 ratio), Pearson correlation −0.51, p = 0.031, n=18.
Percentages of DN CD30+ve T cells present following repeated in vitro allogeneic stimulation of recipient PBMC correlate with graft preservation following lung transplantation.
CD30 expression may have a role in lung transplant tolerance. This may lead to novel tolerance-inducing therapies.
K. Polster, None.