Innate immune response against HPV: Possible crosstalking with endocervical γδ T cells

Cervical carcinoma is significantly associated with the human papillomavirus (HPV). Persistent infection with high risk-HPV is necessary but not sufficient for the development of cervical cancer. It is not fully understood which immunological mechanisms lead to persistence in some patients. During the life cycle, HPV uses excellent immune evasion mechanisms. Keratinocytes, Langerhans cells (LC), dendritic cells (DC), tissue-resident macrophages, and intraepithelial gamma-delta T cells (γδ T cells) are cellular components of the mucosal immune defense of the female genital tract against HPV. γδ T cells, the prototype of unconventional T cells, play a major role in the first line defense of epithelial barrier protection. γδ T cells connect the innate and adaptive immunity and behave like a guardian of the epithelium against any form of damage such as trauma and infection. Any changes in γδ T cell distribution and functional capability may have a role in persistent HPV infection and cervical carcinogenesis in the early phase. Poor stimulation and maturation of APCs (LC/DC) might lead to persistent HPV infection which all point out pivotal role of γδ T cells in HPV persistence. If such an intriguing link is proven, γδ T cells can be used in potential therapeutics against HPV in infected patients.