Expression of TNFalpha by CD3+ and F4/80+ cells following irradiation preconditioning and allogeneic spleen cell transplantation.

Abstract

The pathogenesis of acute graft-versus-host disease (aGVHD) includes tumor necrosis factor-alpha (TNFalpha) expression by macrophages and T cells. However, the temporal comparison of donor vs host cells to TNFalpha expression in response to irradiation conditioning and alloreactivity has not been reported. This study compared intracellular TNFalpha expression in donor vs host spleen T cells and macrophages using a murine model of aGVHD. Total body irradiation conditioning alone resulted in increased frequency of F4/80+/TNFalpha+ cells, but no increase in CD3+/TNFalpha+ cells. Syngeneic transplantation resulted in an increased frequency of F4/80+/TNFalpha+ cells, while CD3+/TNFalpha+ cells increased on days 1 and 3 but declined on day 5. Allogeneic transplantation resulted in an increased frequency of donor CD3+/TNFalpha+ cells, while the frequency of host CD3+/TNFalpha+ cells declined. Similarly, donor F4/80+/TNFalpha+ cells also increased in frequency after allotransplantation, while the frequency of host F4/80+/TNFalpha+ cells was increased on day 1 and declined through days 3 and 5. In absolute cell numbers, CD3+/TNFalpha+ cells were greater than F4/80+/TNFalpha+ cells post allotransplantation. We conclude that (1) both donor and host CD3+ and F4/80+cells are present in the post transplant period and contribute to TNFalpha production and (2) in terms of frequency, the majority of TNFalpha producing cells in the spleen after allogeneic BMT are CD3+.