Predominant donor CD103+CD8+ T cell infiltration into the gut epithelium during acute GvHD: a role of gut lymph nodes.
The existence of donor effector cell subsets responsible for either gut or skin graft-versus-host disease (GvHD) is still undetermined. We examined the trafficking and role of donor CD8(+) intra-epithelial lymphocytes (IELs) in the gut and skin epithelia concerning alpha E beta 7 integrin (CD103) expression, using a rat acute lethal GvHD model. Most CD103(+) donor cells were CD8(+) and showed a proliferative activity in the target epithelia. On the other hand, activated donor T cells in the host lymphoid tissues did not express CD103, indicating the presence of CD8(+) IEL precursors in the lymphoid tissues that may up-regulate CD103 only after migrating to the target organs. At the late stage of GvHD, while >80% of the donor CD8(+) IELs were CD103(+) in the gut epithelium, both CD4(+) and CD103(+)CD8(+) T cells evenly accumulated in the skin epidermis. The CD103 expression by donor CD8(+) IELs especially in the gut was also correlated with the clinical GvHD manifestations. Furthermore, the selective removal of gut lymph nodes (LNs) but not skin LNs suppressed the infiltration of CD103(+) donor IELs in the gut and alleviated intestinal GvHD. In conclusion, CD103(+)CD8(+) donor T cells predominantly infiltrate into the gut epithelium and are responsible for the manifestations of intestinal GvHD. This pathology is at least partly dependent on the gut LNs.
Zhou
Shu
S
Department of Anatomy (Macro), Solution Oriented Research for Science and Technology (SORST) and Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
Ueta
Hisashi
H
Xu
Xue-Dong
XD
Shi
Changde
C
Matsuno
Kenjiro
K
D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D039001:Integrin alpha Chains / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D008198:Lymph Nodes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000528:radiation effects; D008297:Male; D051381:Rats; D013997:Time Factors
D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins