Possible involvement of cytokines, chemokines and chemokine receptors in the initiation and progression of chronic GVHD

Abstract

Chronic GVHD (cGVHD) after allogeneic hematopoietic SCT (HSCT) is characterized by an infiltration of T cells into target organs including the oral mucosa and salivary glands. This study was designed to clarify the molecular mechanism of the local accumulation of pathogenic T cells in cGVHD. The expression of cytokines, chemokines and chemokine receptors in the buccal mucosa (BM), labial salivary glands (LSG) and PBMC from 16 patients with cGVHD after allogeneic HSCT was examined. The mRNA expression of T helper 1 (Th1) and Th2 cytokines, and several chemokines and chemokine receptors was significantly increased in the BM and LSG from cGVHD patients, in comparison with both those in the BM and LSG from controls, respectively, and also with those in the PBMC from cGVHD patients. Furthermore, the mRNA expression of Th2 cytokines, macrophage-derived chemokine and CC chemokine receptor 4 was closely associated with a strong T-cell infiltration in the BM and LSG from cGVHD patients. These results suggest that cGVHD might be initiated and/or maintained by Th1/Th0 cells and thereafter progresses in association with Th2 cell accumulation via the interaction of particular chemokine and chemokine receptors.

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation

“…11 On the other hand, Th2 cells are considered to be responsible for the development of chronic GvHD. [12][13][14] In vitro assays using blood from patients with CLL and a pre-clinical mouse model demonstrated a shift from Th2 toward Th1 dominated CD4 immunity upon exposure to ibrutinib. 10 This report prompted us to establish immune-monitoring for patients who received ibrutinib after alloSCT.…”

Oral chronic graft-versus-host disease: A short review

“…Traditionally, when it targets the immune system, by definition, if seen before Day +100 it is called as acute GVHD (aGVHD), but if it occurs after day 100 it is defined chronic GVHD, however, according to NIH Consensus criteria it is recommended to classify GVHD based on characteristic symptoms and signs rather than a rigid temporal definition [2,3,5,8,10].…”

<b>Pivotal role of duct epithelia in salivary gland </b><b>GVHD </b>

“…In reports of human cases, to avoid invasive clinical examination, assessment of salivary gland lesions had been substituted with oral minor salivary glands (Alborghetti et al, 2005;Prochorec-Sobieszek et al, 2012;Soares et al, 2013). Using biopsies of minor salivary glands of oral mucosa, expression of chemokines and cytokines (Hayashida et al, 2013), infiltration of CD4-positive and CD8-positive T cells (Hiroki et al, 1996;Soares et al, 2005), and expression of HLA-DR, human class II major histocompatibility complex (MHCII) molecule on ductal epithelial cells (Hiroki et al, 1996;Lindahl et al, 1988) were assessed to date, from an immunological point of view. However, because the major salivary glands are composed of a varied mixture of serosal and mucous glands, minor glands might not always reflect pathology of three different major glands, submandibular gland (SMG), parotid gland (PG), and sublingual gland (SLG).…”

“…In humans and in most other species, MHCII is primarily However, kinetics of MHCII on ductal epithelial cells and interactions between ductal cells and T cells were not studied in these human reports. Besides, expression of chemokines and cytokines had been assessed by using whole gland of surrounding oral mucosa, so it is still unclear which cells or tissue components are responsible to secrete these humoral factors in salivary glands (Hayashida et al, 2013).…”