Immunophenotyping fish-to-mouse islet xenograft rejection: a time course study

Area of Science:

• Transplantation immunology
• Xenotransplantation research
• Cellular immunology

Background:

• Tilapia Brockmann bodies (BBs) successfully maintain normoglycemia in diabetic nude mice.
• However, BBs transplanted into euthymic mice undergo rapid rejection, typically within one week.

Purpose of the Study:

• To characterize the cellular infiltrates involved in tilapia xenograft rejection in euthymic mice.
• To understand the immune mechanisms underlying xenograft rejection across a wide phylogenetic barrier.

Main Methods:

• Tilapia BBs were transplanted under the kidney capsule of streptozotocin-diabetic Balb/c mice.
• Graft-bearing kidneys were analyzed at various time points post-transplantation (1, 2, 3, 5 days, and at rejection).
• Immunohistochemical staining was performed to identify macrophages, CD4+ T-cells, CD8+ T-cells, granulocytes (eosinophils), and plasma cells.

Main Results:

• Early (1 day) rejection involved central necrosis and macrophage infiltration.
• Granulocytes, predominantly eosinophils, surrounded the graft by day 2.
• T-cells (CD4+ and CD8+) appeared by day 3, with macrophages massively infiltrating necrotic areas.
• At rejection (5 days), macrophages and eosinophils dominated the graft center, while T-cells were found at the periphery.

Conclusions:

• Cell-mediated immune responses contribute to tilapia xenograft rejection.
• Eosinophils play a significant role in the rejection of these cellular xenografts.
• This study elucidates the cellular dynamics in xenograft rejection across a broad phylogenetic divide.