Interferon-γ Knockout Fails to Confer Protection Against Obliteration in Heterotopic Murine Tracheal Allografts

• Published in: The Journal of heart and lung transplantation Vol. 24; no. 6; pp. 658 - 664
• Main Authors: Batirel, Hasan F., Batirel, Saime, Mitchell, Richard N., Swanson, Scott J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2005; Elsevier Science
• Subjects: Animals; Biological and medical sciences; CD11b Antigen - metabolism; CD4 Antigens - metabolism; CD8 Antigens - metabolism; Disease Models, Animal; Interferon-gamma - physiology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Mice, Knockout; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Trachea - transplantation; Tracheal Diseases - etiology; Tracheal Diseases - metabolism; Tracheal Diseases - prevention & control; Transplantation, Heterotopic - adverse effects; Heart; Rodentia; Homograft; Heterotopic; Cardiovascular disease; Vertebrata; Mammalia; Treatment; Mouse; Animal; Surgery; Graft; Obliteration; Protection; Trachea; Failure; Gamma interferon
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2004.04.013

Interferon-γ, produced by T-helper cells, activates macrophages and increases expression of major histocompatibility complex (MHC) products in acute and chronic rejection. We investigated the role of interferon-γ in murine heterotopic tracheal allografts. Tracheas from BALB/c mice were heterotopically transplanted to BALB/c (12 isografts: 2 weeks [ n = 6] and 4 weeks [ n = 6], C57BL/6 (12 allografts: 2 weeks [ n = 6] and 4 weeks [ n = 6]) and C57BL/6 interferon-γ knockout mice (12 interferon-γ knockout allografts: 2 weeks [ n = 4] and 4 weeks [ n = 8]). BALB/c interferon-γ knockout tracheas were transplanted to C57BL/6 mice (reverse knockout: 4 weeks [ n = 6]) and BALB/c interferon-γ knockout mice (4 weeks [ n = 2]). C57BL/6 tracheas were transplanted to Bm12 mice (MHC Class II mismatch allografts: 4 weeks [ n = 6]). Conventional histology and immunohistochemistry for CD4, CD8 and CD11b were performed. Minimal (<20%) obliteration was seen at 2 weeks in the allograft groups. No obliteration was seen in the isograft groups. However, all allografts were completely obliterated at 4 weeks. Interferon-γ knockout allograft combinations displayed severe rejection characterized by intense intra- and extraluminal infiltration by CD4-, CD8- and CD11b-labeled cells. The MHC Class II mismatch allograft group showed normal epithelium and mild sub-epithelial infiltration by CD4 + cells at 4 weeks (CD8 −, CD11b −). Absence of interferon-γ does not protect the allograft from obliteration. Epithelial destruction by cytotoxic T cells appears to be an important mechanism in the development of obliteration in murine heterotopic tracheal allografts.