CD161+ T Cells as Predictive Markers for Acute Graft-versus-Host Disease

• CD161 expressions on T cell subset were diverse according to the occurrence of GVHD.
• Frequency of CD8+CD161+ cells at engraftment correlated with the severity of GVHD.
• Circulating IL-17 levels at engraftment was associated with the occurrence of GVHD.
• RORγT was more highly expressed in CD4+CD161+ T cells rather than CD8+CD161+ T cells.

CD161 is a type II transmembrane glycoprotein with characteristics of the C-type lectin superfamily, which has recently been shown to promote T cell expansion. In this study, the role of T cells expressing CD161 as a predictor for the occurrence of acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation (SCT) was investigated. Sixty-one patients who underwent first allogeneic SCT were enrolled. At engraftment, the expression of CD3, CD4, CD8, CD161, CD16, and CD56 was analyzed by flow cytometry. After adjusting for potential variables by univariate analysis, we performed a multivariate analysis, which revealed a low frequency of CD8+CD161+ cells (P = .034) and a high ratio of CD4+CD161+ to CD8+CD161+ cells (P = .001) were associated with the occurrence of aGVHD with a grade of ≥ II. Moreover, the frequency of CD8+CD161+ T cells was negatively correlated with aGVHD grade. A separate analysis for visceral aGVHD showed similar results, with a low frequency of CD8+CD161+ T cells (P = .031) or a high ratio of CD4+CD161+ to CD8+CD161+cells (P < .001), indicating a high risk. Also, the predictive role of serum IL-17 levels for the occurrence of aGVHD was identified, and RORγT was more highly expressed in CD4+CD161+ T cells than in CD8+CD161+ T cells after allogeneic SCT (P = .032). Although our study was limited by the heterogeneity and small number of patients, these results suggest that the CD8+ subset of CD161+ T cells may have regulatory effects and that they provide a basis for predicting the occurrence of aGVHD after allogeneic SCT.