Depletion of CD4+ cells exacerbates the cutaneous response to acute and chronic UVB exposure

J Invest Dermatol. 2007 Jun;127(6):1507-15. doi: 10.1038/sj.jid.5700746. Epub 2007 Mar 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / radiation effects*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / radiation effects
  • Chronic Disease
  • Dermatitis / epidemiology
  • Dermatitis / immunology*
  • Dinoprostone / metabolism
  • Female
  • Immunocompromised Host / immunology
  • Keratinocytes / cytology
  • Mice
  • Mice, Hairless
  • Neutrophils / cytology
  • Neutrophils / radiation effects
  • Peroxidase / metabolism
  • Risk Factors
  • Skin / immunology*
  • Skin / radiation effects*
  • Skin Neoplasms / epidemiology
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays / adverse effects*


  • Tumor Suppressor Protein p53
  • Peroxidase
  • Dinoprostone