title: Depletion of CD4+ cells exacerbates the cutaneous response to acute and chronic UVB exposure.
abstract: Solid organ transplant recipients have a 60-250-fold increased likelihood of developing sunlight-induced squamous cell carcinoma (SCC) compared with the general population. This increased risk is linked to the immunosuppressive drugs taken by these patients to modulate T cell function, thus preventing organ rejection. To determine the importance of T cells in the development of cutaneous SCC, we examined the effects of selectively depleting Skh-1 mice of systemic CD4+ or CD8+ T cells, using monoclonal antibodies, on ultraviolet B (UVB) radiation-induced inflammation and tumor development. Decreases in systemic CD4+ but not CD8+ T cells significantly increased and prolonged the acute UVB-induced cutaneous inflammatory response, as measured by neutrophil influx, myeloperoxidase activity, and prostaglandin E2 levels. Significantly more p53+ keratinocytes were observed in UVB-exposed CD4-depleted than in CD4-replete mice, and this difference was abrogated in mice depleted of neutrophils before UVB exposure. Increased acute inflammation was associated with significantly increased tumor numbers in CD4-depleted mice chronically exposed to UVB. Furthermore, topical treatment with the anti-inflammatory drug celecoxib significantly decreased tumor numbers in both CD4-replete and CD4-depleted mice. Our findings suggest that CD4+ T cells play an important role in modulating both the acute inflammatory and the chronic carcinogenic response of the skin to UVB.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hatton
authors.forename: Allison
authors.initials: A
authors.lastname: Parent
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Tober
authors.forename: Tyler
authors.initials: T
authors.lastname: Hoppes
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wulff
authors.forename: F Jason
authors.initials: FJ
authors.lastname: Duncan
authors.forename: Donna F
authors.initials: DF
authors.lastname: Kusewitt
authors.forename: Anne M
authors.initials: AM
authors.lastname: VanBuskirk
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Oberyszyn
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects; D002908:Chronic Disease; D003872:Dermatitis / Q000453:epidemiology / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D016867:Immunocompromised Host / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008812:Mice, Hairless; D009504:Neutrophils / Q000166:cytology / Q000528:radiation effects; D009195:Peroxidase / Q000378:metabolism; D012307:Risk Factors; D012867:Skin / Q000276:immunology* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016159:Tumor Suppressor Protein p53; D009195:Peroxidase; D015232:Dinoprostone