Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection.
As biopsies are not taken at the time of human corneal allograft rejection, most information on the early cellular changes in rejection is from animal models. We examined the phenotype of alloreactive cells present in the human anterior chamber during corneal graft rejection by flow cytometry and quantified aqueous humor levels of cytokines and chemokines using cytometric bead array. Aqueous and peripheral blood samples were taken from patients with graft endothelial rejection (n = 11) and from control patients undergoing cataract surgery (n = 8). CD45(+)CD4(+), CD45(+)CD8(+) and CD45(+)CD14(+) cells were found in aqueous during rejection; no CD45(+) cells were seen in control samples. Higher proportions of CD45(+) cells found in aqueous during rejection were CD14(+), denoting monocyte/macrophage lineage, than were CD4(+) or CD8(+). Large elevations were seen in aqueous levels of IL-6, MCP-1 and IP-10 during rejection compared with controls; smaller but still statistically significant increases were seen in MIP-1alpha and eotaxin. The role of CD14(+) cells in allorejection is unclear as is the potential of these chemokines and their receptors as therapeutic targets. Aqueous humor samples offer a unique opportunity to analyze components of the allogeneic response in direct contact with donor tissue but without artifacts inherent in examination of tissue.
Department of Ocular Immunology, UCL Institute of Ophthalmology, London, UK. t.flynn@ucl.ac.uk
T H
TH
Flynn
N A
NA
Mitchison
S J
SJ
Ono
D F P
DF
Larkin
D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D018925:Chemokines / Q000032:analysis* / Q000276:immunology; D016039:Corneal Transplantation; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010641:Phenotype
C111835:CCL2 protein, human; D015704:CD4 Antigens; D016827:CD8 Antigens; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human