Study design

The study was initiated to determine whether certain T cell–derived cytokines could separate GvHD from GvL and so may represent promising novel therapeutic targets for the treatment of hematologic malignancies. To achieve this aim, we used two different experimental models of GvHD, an experimental model of GvL, and samples from human subjects. For animal studies, 8- to 12-week-old mice were used. All animal experiments were approved by local authorities (Swiss Cantonal Veterinary Office) and performed under the appropriate experimental licenses (76/2012 and 052/2015). Animals were randomly assigned into the experimental groups, and in-life clinical score was performed in a blinded fashion and image analysis processing on organ sections. Sample size and disease end time points were selected on the basis of previous studies. Flow cytometry, histopathological analysis, MLRs, killing assays, and cytokine analysis were performed to characterize the GvHD/GvL target organs. The effects of the specific GM-CSF blocking antibody on clinical score were assessed by investigators who were blinded to the treatment. To perform reliable statistical analysis, three independent experiments were conducted for each data shown in the manuscript, unless differently indicated in the figure legends.

All human samples were collected after approval by the Ethics Committee of the Albert-Ludwigs University Freiburg, Germany (protocol no. 267/11) following written informed consent. We performed immunohistochemistry and quantitative reverse transcription polymerase chain reaction on the gut biopsies and multiparameter flow cytometry on the PBMCs. Primary data are located in table S5. Also, clinical features of patients can be found in tables S1 to S4. The scoring system used for allo-HCT mice is described in table S6, and the phenotypical analysis of human PBMCs in table S7.