Host skin T cells survive stem cell transplant conditioning and are functional during acute GVHD

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.82-82.13
• Main Authors: Divito, Sherrie J, Elco, Christopher, Guleria, Indira, Milford, Edgar, Cutler, Corey, Kupper, Thomas S
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.82.13

Graft-versus-host-disease (GVHD) is a major cause of morbidity and mortality in stem cell transplantation (SCT). Acute GVHD is thought to be mediated by donor T cells that target and destroy host tissues. Studies into the host immune system are limited, as it is assumed that host T cells in peripheral tissues such as skin are depleted by conditioning regimens in parallel to T cells in lymphoid organs and blood. However, it is recently appreciated that a high number of memory T cells reside long-term within the organs most affected by GVHD. We investigated whether host skin T cells survive SCT conditioning and are present during acute GVHD. To do so, excess skin biopsy tissue was obtained from patients with acute skin GVHD who had undergone myeloablative or non-myeloablative conditioning and allogeneic SCT with sex-mismatched donor cells. Tissue was stained for T cell markers via immunofluorescence concurrently with in situ hybridization for the X and Y chromosomes. All seventeen patients studied demonstrated persistence of host T cells in skin, often in equal or greater numbers than donor T cells. Host skin T cells survived regardless of myeloablative or non-myeloablative conditioning, of patient age, and of day post-SCT (samples ranged from 12–213 days post-SCT). Comparatively, blood T cell chimerism was 100% donor in nearly all samples, indicating diverging effects of conditioning on T cell compartments. Skin host T cells demonstrated pro-inflammatory cytokine production. These results provide a novel avenue of research into GVHD pathobiology and suggest that alternative conditioning regimens should be employed if host skin T cells are to be targeted.