Evidence that T-helper type 2 cell-derived cytokines and eosinophils contribute to acute rejection of orthotopic corneal xenografts in mice.
BACKGROUND
Because guinea pig corneal xenografts are rejected acutely (within 16 days) in mouse eyes by a T-cell-dependent mechanism, the authors wished to determine the functional phenotype of CD4+ effector T cells.


METHODS
Orthotopic corneal xenotransplantation was performed from strain 13 guinea pigs to BALB/c mice. Grafted eyes were removed at specified times and examined histologically or subjected to cytokine and chemokine mRNA analysis using a multi-probe ribonuclease protection assay. Draining cervical lymph node cells were harvested at specified times and stimulated in vitro with x-irradiated strain 13 guinea pig spleen cells. Supernatants were assayed by enzyme-linked immunosorbent assay for content of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, and IL-10 and cells were used for mRNA analysis.


RESULTS
Rejected corneal xenografts were heavily infiltrated with polymorphonuclear leukocytes, the majority of which were eosinophils. These eyes contained mRNA for IL-4, IL-6, IL-10, IL-13, IL-15, and IFN-gamma. When stimulated with guinea pig spleen cells, T cells from draining cervical lymph nodes secreted primarily IL-4, IL-5, IL-10, and IFN-gamma. Eotaxin was overexpressed in eyes with rejected corneal xenografts.


CONCLUSIONS
Acute rejection of corneal xenografts in mice is mediated by T cells that display a mixed T-helper (Th) type 2/Th1 phenotype and secrete eotaxin, an eosinophil chemoattractant. Eosinophil-dependent xenograft rejection bears similarities to immune elimination of parasites.
Tanaka
Kazumi
K
Department of Ophthalmology, Yokohama City University of Medicine, Yokohama, Japan.
Yamagami
Satoru
S
Streilein
J Wayne
JW
D000208:Acute Disease; D000818:Animals; D015478:Antigens, Heterophile / Q000378:metabolism; D003315:Cornea / Q000473:pathology; D016039:Corneal Transplantation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils; D005123:Eye / Q000378:metabolism; D015870:Gene Expression; D006084:Graft Rejection / Q000209:etiology*; D006168:Guinea Pigs; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009333:Neck; D018418:Th2 Cells / Q000378:metabolism*; D014183:Transplantation, Heterologous
D015478:Antigens, Heterophile; D016207:Cytokines