Kinetics of IFN-γ and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease

Abstract

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-γ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 → BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 → BALB.B GVHD model, we showed that the production of IFN-γ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-γ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

Skewed Dendritic Cell Differentiation of MyD88-Deficient Donor Bone Marrow Cells, Instead of Massive Expansion as Myeloid-Derived Suppressor Cells, Aggravates GVHD

“…MHC/MiHA-fully mismatched GVHD models, for example, B6→B6D2F1, have shown drastic early mortality (MST=12.5–15.0 days) after MyD88-KO BMT, as described in our previous study (22), hampering stable longitudinal mechanistic studies. Therefore, we considered that slowly progressing GVHD models such as MiHA-mismatched models would be appropriate for consistent longitudinal BLI analysis; therefore, we used the B6→BALB.B model in which immune kinetics has been well characterized (20263435). To test whether GVHD aggravation in MyD880-KO BM recipients would be reproduced by use of Luc Tg BM, the Luc Tg BM alone or together with WT T cells were transplanted into BALB.B mice irradiated with a lethal dose (900 cGy) for an allo non-GVHD or GVHD setting, respectively.…”

Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen

“…BM cells isolated from the femur and tibia of gender-matched donors were depleted of T cells by MACS and 5 × 10 6 T cell-depleted BM (TCD-BM) cells were transferred i.v. into recipients 5 h after the second irradiation as previously described 57 , 58 . EL4 cells were purchased from ATCC (TIB-39; Rockville, MD, USA), and transduced to express H60, H60 and Luciferase, or H60 and Thy1.1 (H60 + EL4) or transduced with empty vector 32 .…”

Long-term consumption of sugar-sweetened beverage during the growth period promotes social aggression in adult mice with proinflammatory responses in the brain

“…After washing each well four times with washing buffer, 200 μl of substrate solution prepared with equal amounts of stabilized hydrogen peroxide and tetramethylbenzidine was added for a 20 min reaction in the dark. The reaction was quenched by adding 50 μl stop solution (2NH 2 SO 4 )64.…”