Rejection of allogenic uterus transplant in the mouse: Time-dependent and site-specific infiltration of leukocyte subtypes

Abstract

BACKGROUNDAnimal models of uterus transplantation are being developed ahead of a possible treatment for absolute uterus infertility in women. Our knowledge of inflammatory cell involvement in acute rejection of a uterus transplant is limited; therefore, we examined the pattern of invasion of leukocyte subtypes into an allogeneic uterus transplant.METHODSThe uterus and its vasculature were removed from BALB/c mice and transplanted into C57Bl/6 recipient mice at a heterotopic position, with the native uterus left in situ. Both uteri were removed on post-operative day 2 (D2, n = 5), D5 (n = 5) and D10 (n = 6). Immunohistochemistry for neutrophilic granulocytes, macrophages, cytotoxic CD8+ T-cells, CD4+ T-helper cells and B-cells was performed and cell density was evaluated in both myometrium and endometrium.RESULTSNeutrophil density was increased in graft versus native uteri at D5 and D10 in myometrium and D10 in endometrium, and in endometrium was higher in the D5 than D2 graft (all P < 0.05). Infiltration of macrophages occurred from D2 in myometrium and from D5 in endometrium (P < 0.05, graft versus native). Density of CD8+ cytotoxic T-cells increased in the graft versus native uteri at D5 in both uterine layers and for the graft versus D2 density (P < 0.01). In contrast, CD4+ T-helper cells increased only transiently in graft endometrium at D5 (P < 0.05). Overall CD19 + B-cell density was low, with no time-dependent changes in graft myometrium or endometrium.CONCLUSIONSAcute rejection of an allogeneic uterus transplant in the mouse involves influx of predominately neutrophils, macrophages, CD8+ T-cells and CD4+ T-cells between D2 and D5 post-operatively.