Protective and pathological roles of virus-specific and bystander CD8+ T cells in herpetic stromal keratitis.
Herpetic stromal keratitis (HSK), resulting from corneal HSV-1 infection, represents a T cell-mediated immunopathologic lesion. In T cell transgenic mice on a SCID or RAG knockout background, the T cells mediating lesions are unreactive to viral Ags. In these bystander models, animals develop ocular lesions but are unable to control infection. Transfer of HSV-immune cells into a CD8(+) T cell bystander model resulted in clearance of virus from eyes, animals survived, and lesions developed to greater severity. However, the adoptively transferred CD8(+) T cells were not evident in lesions, although they were readily detectable in the lymphoid tissues as well as in the peripheral and CNS. Our results indicate that viral-induced tissue damage can be caused by bystander cells, but these fail to control infection. Immune CD8(+) T cells trigger clearance of virus from the eye, but this appears to result by the T cells acting at sites distal to the cornea. A case is made that CD8(+) T cell control is expressed in the trigeminal ganglion, serving to curtail a source of virus to the cornea.
Banerjee
Kaustuv
K
Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Biswas
Partha Sarathi
PS
Kumaraguru
Udayasankar
U
Schoenberger
Stephen P
SP
Rouse
Barry T
BT
D019264:Adoptive Transfer; D000818:Animals; D024201:Bystander Effect / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D002908:Chronic Disease; D003319:Corneal Stroma / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020803:Encephalitis, Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D016849:Keratitis, Herpetic / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018139:Simplexvirus / Q000276:immunology*; D019562:Viral Load
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein