IL-10 and natural regulatory T cells: two independent anti-inflammatory mechanisms in herpes simplex virus-induced ocular immunopathology.
Two prominent anti-inflammatory mechanisms involved in controlling HSV-1-induced corneal immunopathology (stromal keratitis or SK) are the production of the cytokine IL-10 and the activity of natural regulatory T cells (nTregs). It is not known whether, under in vivo conditions, IL-10 and nTregs influence the corneal pathology independently or in concert. In the current study using wild-type and IL-10(-/-) animals, we have assessed the activity of nTregs in the absence of IL-10 both under in vitro and in vivo conditions. The IL-10(-/-) animals depleted of nTregs before ocular infection showed more severe SK lesions as compared with the undepleted IL-10(-/-) animals. In addition, nTregs purified from naive WT and IL-10(-/-) animals were equally able to suppress the proliferation and the cytokine production from anti-CD3-stimulated CD4(+)CD25(-) T cells in vitro. Furthermore, intracellular cytokine staining results indicated that nonregulatory cells expressing B220 and CD25 markers were the major IL-10-producing cell types in the lymphoid tissues of HSV-infected mice. In contrast, in the infected corneas, cells with the CD11b(+)Gr1(+) phenotype along with a minor population of Foxp3(-)CD4(+) and a few F4/80(+) cells produced IL-10. Our current investigations indicate that at least two independent anti-inflammatory mechanisms are involved in limiting the corneal lesions in SK, both of which may need to be modulated to control SK therapeutically.
Sarangi
Pranita P
PP
Comparative and Experimental Medicine Program, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
Sehrawat
Sharvan
S
Suvas
Susmit
S
Rouse
Barry T
BT
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D049109:Cell Proliferation; D003316:Corneal Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000821:virology
D015703:Antigens, CD; D016753:Interleukin-10; D017493:Leukocyte Common Antigens