Prolonged acceptance of skin grafts induced by B cells places regulatory T cells on the histopathology scene.
The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance has been claimed in different models. In skin grafts, naive B cells were shown to induce graft tolerance. However, neither the contribution of Treg cells to B cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to tolerize female animals, we show that skin graft tolerance is dependent on CD25+ Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from IL-10-deficient mice were able to induce skin graft tolerance while Treg depletion of the host inhibited 100% graft survival. We questioned how Treg cell-mediated tolerance would impact on histopathology. B cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4+ cells were FoxP3+ Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4 cells with a Treg:Teff ratio below 1:1. These results render Treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.
Programa de Medicina Experimental, Coordenação Geral Técnico-Científica, Instituto Nacional de Câncer, Rio de Janeiro, Brasil.
S
S
Langier
R G
RG
Galvani
A P G
AP
Alves
R
R
Fidelis
P H C
PH
Nunes
M H
MH
Silva
L R
LR
Castilho
J P
JP
Monteiro
A
A
Bonomo
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D023001:Transplantation Tolerance / Q000276:immunology*
D051858:Forkhead Transcription Factors