Natural killer activity in (C57BL/6 × DBA/2)F₁ hybrids undergoing acute and chronic graft‐vs.‐host reaction

Abstract

The present findings demonstrate that a total i.v. transfer of 100 X 10(6) C57BL/6 (B6) parental spleen cells into untreated (C57BL/6 X DBA/2)F1 hybrids (B6D2F1) resulted in acute runting, which was associated with a significantly elevated graft-vs.-host (GVH) index over a one-month period following GVH induction. Furthermore, this B6-induced acute GVH disease was associated with a marked depression of natural killer (NK) cell activity (spleen and peripheral blood) (with or without addition of mouse fibroblast interferon), which correlated with lymphoid cell hypocellularity, prominent splenic extramedullary hematopoiesis (EMH), and parallel depressions of both concanavalin A- and lipopolysaccharide-induced mitogenesis. Significantly increased killing by antibody-dependent cellular cytotoxicity of antibody-coated chicken red blood cells, as well as increased T cell killing of the NK-insensitive cell line P815 (as compared to the significantly decreased killing of the NK-sensitive cell line YAC-1) was also observed in the spleens of this 100 X 10(6) B6-injected F1 group. In marked contrast to this 100 X 10(6) B6-injected acute GVH group, untreated mice injected i.v. with the same or greater numbers of parental DBA/2 spleen cells (100 X 10(6)-150 X 10(6) DBA/2 spleen cells) exhibited a milder and more chronic form of GVH disease, which was not associated with a significant decrease of NK activity. It was of considerable interest that a total i.v. transfer of 50 X 10(6) B6 spleen cells (i.e. one-half of that required to produce acute GVH, markedly depressed NK, and prominent splenic EMH) into B6D2F1 hybrids also resulted in a more chronic form of GVH disease, but was associated with significantly increased levels of NK activity at two weeks post GVH induction.

Natural Killer Cells in Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation

“…Pattengale and coworkers were the first to demonstrate in murine models that acute but not chronic GvHD induce a marked decrease in NK cell activity associated with an impaired production of IFN-γ (80). NK cell reconstitution appears to be significantly delayed by acute GvHD in mice (81) and by acute and chronic GvHD in humans (42, 82–85).…”

Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation

“…We confirmed that IL-2 administration to non-transplanted normal mice increased NK cells in an IL-2 dose-dependent manner, however, IL-2 administration to allo-transplanted recipient mice did not increase NK cells in the experimental HSCT used in this study ( Supplemental Figure S4 ). In fact, previous studies have shown that more than 50 million spleen cells need to be infused at transplant in order to observe NK cells in the B6-into-B6D2F1 system ( 42 , 43 ). In our experimental setting, we infused 5 million spleen cells and it appears to be not enough to evaluate NK cells after transplant.…”

Augmentation of Natural Killer Cell Activity by Anti‐Host Delayed‐Type Hypersensitivity during the Graft‐versus‐Host Reaction in Mice

“…These findings thus extend earlier observations by providing a mechanism for the augmented NK activity demonstrated in GVH reaction [3., 20,29,33]. In these studies, unirradiated F, hybrid mice were used as hosts for the GVH reaction, and we proposed that an F| response to the injected parental cells might be one stimulus lor the activation of NK cells |3|, F, miee recognize and reject haemopoietic cells from certain parental strains [6,8], and it is probable that host NK cells mediate this resistance |8, 14,21.44].…”