Year: 2016
Type: article
Abstract: T cells are central to the biology of chronic graft-versus-host disease (cGVHD), a major barrier to successful allogeneic hematopoietic stem cell transplantation (AHSCT). In a pre-clinical model of cGVHD we characterized target organ T cell subsets in the evolution of cGVHD. Histologically, the small intestines of AHSCT recipients had a lymphocytic infiltrate prior to clinical onset of cGVHD. Three anatomically distinct layers of the small bowel were evaluated by flow cytometry: intraepithelial lymphocytes (IEL), lamina propria (LP), and Peyer’s patches (PP). In normal mice and syngeneic recipients, LP contained the greatest number of CD4+ T cells compared to IEL and PP, and CD8+ T cells outnumbered CD4+ T cells. In contrast, in allogeneic recipients, CD4+ T cells were greatly increased in the IEL, with numbers that exceeded those within the LP, also outnumbering CD8+ T cells. The predominant phenotype of CD4+ T cells in the allogeneic IEL and LP was T effector memory (Tem). Interestingly, T regulatory (Treg) number in both IEL and LP was increased in the allogeneic setting once cGVHD was clinically evident, but not early in cGVHD pathogenesis when mice remained asymptomatic. Despite an increased Treg number in the allogeneic IEL associated with cGVHD, the Treg to Tem ratio was reduced compared to the syngeneic setting, similar to other target organs. This ratio may represent an early marker of cGVHD as it precedes development of frank cGVHD. Furthermore, double positive (DP) cells, which represent a unique innate lymphoid intestinal population, were increased in the IEL and reduced in the LP layers of AHSCT recipients. In summary, the IEL, intestinal layer closest to the gut lumen, appears to be the primary site of allogeneic CD4+ T cell infiltrates, with a reduced Treg to Tem ratio, and an increased number of DP lymphocytes.
Institutions: National Institutes of Health, National Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2509260530