title: Treg depletion attenuates the severity of skin disease from ganglionic spread after HSV-2 flank infection.
abstract: Regulatory T cells (Tregs) attenuate lesion severity and disease after HSV ocular or genital infection, but their role in cutaneous infection remains unclear. Treg depletion (anti-CD25 mAb in C57BL/6 mice or diphtheria toxin (DT) in DEREG mice) prior to tk-deficient HSV-2 flank infection significantly decreased skin lesion severity, granulocyte receptor-1(Gr-1(+)) cell number, and chemokine (KC) expression in the secondary skin, but significantly increased immune effectors and chemokine expression (MCP-1, KC, VEGF-A) in the draining LN, and activated, interferon-γ producing CD8(+)T cells in the ganglia. Treg depletion also significantly reduced HSV-2 DNA in the ganglia. Thus, Tregs increase the severity of recurrent skin lesions, and differentially alter chemokine expression and immune effector homing in the skin and LN after cutaneous infection, and limit CD8(+) T cell responses in the ganglia. Our data suggests that effects of Treg manipulation on recurrent herpes lesions should be considered when developing Treg mediated therapeutics.
authors.affiliation: Centres for Perinatal Infection Research and Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Locked Bag 4001, Westmead, NSW 2145, Australia. Electronic address: marian.fernandez@health.nsw.gov.au.
authors.forename: Marian A
authors.initials: MA
authors.lastname: Fernandez
authors.forename: Uet
authors.initials: U
authors.lastname: Yu
authors.forename: Geoff
authors.initials: G
authors.lastname: Zhang
authors.forename: Rose
authors.initials: R
authors.lastname: White
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Jones
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005724:Ganglia / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D047589:Leukocyte Reduction Procedures; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology / Q000473:pathology; D017193:Skin Diseases, Viral / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Chemokine; Flank infection; Ganglia; Herpes simplex virus; Mice; Regulatory T cells; Skin