1. ¹Department of Pathology, The Ohio State University, Columbus, Ohio, USA
2. ²Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA
3. ³Department of Surgery, Division of Surgical Oncology, The Ohio State University, Columbus, Ohio, USA

Correspondence: Dr Tatiana M. Oberyszyn, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210, USA. E-mail: oberyszyn.1@osu.edu

⁴These authors contributed equally to this work

Received 26 May 2006; Revised 27 October 2006; Accepted 14 December 2006; Published online 15 March 2007.

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.