Islet xenograft rejection in absence of CD8+ T cells does not require either interferon-gamma or interleukin-5.
We recently demonstrated that interleukin-5 and eosinophils mediate rejection of skin allografts when CD8+ T cell-dependent and Th1-type CD4+ T cell-dependent pathways are not functional. The purpose of this study was to determine whether a similar mechanism might be operative during rejection of rat islet xenografts in mice. First, we observed that eosinophils indeed infiltrate rejected islet grafts together with CD4+ and CD8+ T cells. CD8+ T cell depletion significantly enhanced graft survival and a further prolongation of islet function was obtained in combination with interferon-gamma neutralization. However, islet rejection characterized by prominent eosinophil and macrophage infiltration still occurred in this setting. Although eosinophil infiltrates were dramatically reduced in interleukin-5 deficient mice, the ability of these animals to reject islet xenografts under CD8+ T cell depletion and interferon-gamma neutralization was similar to that of wild-type mice. We conclude that in absence of CD8+ T cells and interferon-gamma, macrophages, but not eosinophils, mediate rejection of rat-to-mouse islet xenografts.
Department of Endocrinology, Hĵpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. lcrenier@ulb.ac.be
Laurent
L
Crenier
Alain
A
Le Moine
Robert
R
Kiss
Willy J
WJ
Malaisse
Michel
M
Goldman
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology; D005260:Female; D006084:Graft Rejection; D007371:Interferon-gamma / Q000502:physiology*; D015848:Interleukin-5 / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D014183:Transplantation, Heterologous / Q000276:immunology*
D015848:Interleukin-5; D007371:Interferon-gamma