Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand.

TLDR

Anti‑CD40L antibody blocks host T‑cell costimulatory signals to donor lymphocytes or islet grafts. Combined allogeneic small lymphocytes plus anti‑CD40L induced indefinite pancreatic islet allograft survival in 37 of 40 recipients, a donor‑antigen‑specific effect far superior to either treatment alone, while anti‑CD40L alone achieved 40% indefinite survival.

Abstract

Combined treatment with allogeneic small lymphocytes or T-depleted small lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite pancreatic islet allograft survival in 37 of 40 recipients that differed from islet donors at major and minor histocompatibility loci. The effect of the allogeneic small lymphocytes was donor antigen-specific. Neither treatment alone was as effective as combined treatment, although anti-CD40L by itself allowed indefinite islet allograft survival in 40% of recipients. Our interpretation is that small lymphocytes expressing donor antigens in the absence of appropriate costimulatory signals are tolerogenic for alloreactive host cells. Anti-CD40L antibody may prevent host T cells from inducing costimulatory signals in donor lymphocytes or islet grafts.