Increased Production of the Inflammatory Cytokine IL12p70 by Activated Human Blood Dendritic Cells Is Associated with Increased Severity of Acute Graft Vs Host Disease Post Allogeneic Hemopoietic Cell Transplantation

Dendritic cells (DC) are centrally involved in the initiation of acute graft versus host disease (GVHD) after allogeneic hemopoietic cell transplantation (alloHCT). We have shown that the activation status of peripheral blood CD11c+ myeloid DC, as assessed by CMRF-44 antigen expression, is highly associated with the occurrence and severity of acute GvHD (Transplantation 2007;83: 839–846). However, very little is known about the function of DC after human alloHCT. We examined the relationship between DC functional properties and the severity of acute GvHD.

Peripheral blood CD11c+ myeloid DC from 12 patients were studied weekly up to 8 weeks post transplant for production of IL2, IL4, INFg, IL10 and IL12 using an intracellular cytokine flow assay. Mixed lymphocyte reactions using flow sorted patient DC and third party T cells were used to assess allogeneic immune responses induced by recipient DC in 5 patients.

IL12 was the only cytokine detected in post transplant DC. Five of 12 patients developed grade II-IV GvHD, the remaining 7 patients developed either no aGvHD or only grade I. In comparison with pre-transplant levels of expression of IL12, patients with grade II-IV GVHD had a significantly higher percentage of CD11c+ DC expressing IL12 (median 15.1%, range 11.2–20.9%) as compared to patients with grade 0-I GvHD in whom there was no change from baseline values (median 6.6% range 2.8–8.9%) p=0.0025. Increased expression of IL12 was observed in CD11c+ DC commencing at day 25 post transplant. Interestingly, analysis of 5 paired samples comparing sorted DC from normal donors with sorted DC from peripheral blood at day +30 post-transplant showed a marked reduction (measured by thymidine uptake from 60% to 90%) in the capacity of post-transplant donor DCs to stimulate 3^rd party lymphocyte proliferation. None of these patients developed clinically significant aGvHD.

Production of IL-12p70 by CD11c+ myeloid DC correlates with severity of GvHD despite impaired capacity of these cells to elicit third party proliferative responses.

No relevant conflicts of interest to declare.