Long-term survival of a transplant is improved in the presence of NK cells.

If immune cells are an army, then a graft transplant is a foreign invasion. New work by Yu et al. on page 1851 shows that antigen-presenting cells (APCs) from the graft are rapidly killed by the host's first line of defense: natural killer (NK) cells. But far from hindering the chance of graft survival, this battle actually improves it.

NK cells are known to improve the chance of graft survival, but how they do this was unknown. Li's team wanted to know what happens to graft APCs when NK cells are absent.

Using mice that lacked a full-blown rejection response (because they lacked lymphocytes), the team were able to follow the fate of donor APCs for longer than would normally be possible. They found that in the absence of NK cells, donor APCs could roam free in the host, as confirmed by their presence in spleen, liver, and lung. In the presence of NK cells, however, injected or graft-derived APCs were completely eliminated from the host.

The team reasoned that immediate destruction of the APCs by NK cells was preventing a more vigorous anti-APC response by host lymphocytes. To confirm this, they restored the T lymphocyte population of the mice and showed that, in the absence of NK cells, APCs activated robust and persistent T cell proliferation and IFN-γ production—marks of a ferocious immune response. But in the presence of NK cells this T cell activation was, as predicted, markedly reduced.

The daily immunosuppressants that transplant patients must take “are designed to suppress T cells,” says lead researcher Xian Li, “but we don't know if they are also suppressing NK cells.” Drugs that specifically suppress T cells but boost host NK cells might therefore improve the outcome for transplant patients.