Researchers from the University of Washington and Fred Hutchinson Cancer Research published a study in Nature based to demonstrate the identification of immunological role of a class of cytotoxic T cells in genital herpes. They identified the cells to be CDT cells that primarily exist in the skin of genital region and mucosa. These cells inhibit the recurrence of genital herpes. Since they suppress the replication of the HSV-2 virus, at the site of recurrence they also prevent symptoms in the patient.
Genital herpes is a sexually transmitted disease affecting more than 24 million people in the US and 60-80 million people worldwide (World Health Organization, 2013). The disease is passed on following sexual contact with an infected person. This study describes how CDimmune cells that live in genital skin and mucosa prevent the reoccurrence of genital herpes outbreaks and potentially could be used as a vaccine against this disease.
HSV-2 (herpes simplex virus-2), which belongs to the herpes virus family (Herpesviridae), is responsible for transmission of genital herpes a highly contagious disease, that affects almost 15% of people between the ages of 14-49 years in the US. A person gets infected following sexual contact with an infected individual. Following infection with HSV-2 virus, “vesicles” appear on the outer surface of the genital organs (Beauman, 2005). These vesicles then appear as lesions which are often painful. It usually takes a few weeks for the lesions to heal. Following the initial, “primary infection”, the virus enters a phase of latency. It lies dormant in neuronal cells when the patient has no symptoms. However, patients infected with HSV-2 can have outbreaks or recurrence of the symptoms at any time. The entry of the HSV-2 virus into the host cells involves binding of proteins (glycoprotein) on the surface of HSV-2 virus to certain receptors on membrane of host’s cell. Following entry into the host cells the virus particle inserts its genetic material to the DNA of the host. This allows for replication of virus particles. Cell based immunity involves activation and proper functioning of T cells or T lymphocytes (white blood cells). CD8 cells are a kind of T cells that are also known as cytotoxic T cells. Early in the process of getting infected by viral particle, the infected (host) cells exhibit viral peptide fragments on their class I surface molecules. CD8 or CTLs that recognize these peptide fragment (antigen) bind to it through their T cell receptor and can destroy the infected cells before multiple copies of viruses are produced in that infected cell. In general, the function of CD8+ T cells is to guard the cells of the body, prepared to kill any cells that exhibit symptoms of being infected.
CD8 +T and CD8 +T are subtypes of the CD8, cytotoxic T cells. Prior to this study, the CD8 +T cells were mainly known to exist in the gut mucosa. The significance of immunologic role of CD+ T cells was not appreciated; in fact little was known about their biological function. Most of the research was carried on the role and working of CD + T cells that are predominantly present in the circulating blood. In the study published by Zhu and Corey, the authors have discovered a very important role for the CD8 + T cells. They report for the first time the existence of the CD8 + T cells in the genital skin and mucosa. The authors very elegantly demonstrate the key mechanism as to why many of the HSV-2 recurrences are without symptoms. It is the “long-term” presence of the CD8 + T cells usually at the site of initial HSV-2 infection that usually results in asymptomatic outbreak. These immune surveillant cells are present at the critical, initial site of infection; the dermis-epidermis junction. The dermis-epidermal junction is the site of connection between the dermis (outer layer of skin) and epidermis (the inner/tissue layer right under the dermis). Dermis-Epidermis junction is the site of many key biological functions. Exchange of nutrients and absorption, communication between cells, repair of injury and some other skin functions occur at the dermis epidermis junction. Many of HSV-2 viruses are in an inactive form when they remain latent in the sensory neuronal cells. The latent virus can get activated following a trigger such as stress. Following activation, the HSV-2 viruses are released at the site of nerve endings. It is at these nerve endings of genital skin and mucosa that the CD8 +T cells are present. The CD8 +T cells efficiently contain and check reactivation of HSV-2 associated with the outbreak. Dr Corey, the lead author of the study hypothesizes that if the efficacy of these CD8 +T cells is enhanced, there is a possibility that these immune cells could effectively prevent the infection by the HSV-2 in the first place (Zhu & Corey, 2013).
The only treatment possible against genital herpes is anti-retroviral drugs. The effectiveness of the anti-retroviral therapy against HSV-2 is limited. The other complication associated with genital herpes is the possibility of transmission of virus from the mother to her child (newborn herpes) at the time of birth. Newborn herpes is one of the most common infections passed from mother to babies.
The real life significance of this study lies in the fact that a novel method or mode of vaccine development against HSV-2 based on the discovery of CD8 +T is postulated. Protein sequences present on the CD8 +T cells would provide epitopes to be used as antigen for development of vaccine. I think their contribution also lies in the fact that they have demonstrated a unique mechanism by which our own immunity (by means of CD8 +T cells) works to control the symptoms and complications associated with genital herpes outbreak. There is a possibility that these cells or cells with similar mode of action might be involved in some day controlling transmission of other type of dermal and mucosal infection and possibly HIV infection.
Fred Hutchinson Cancer Research Center (2013, May 8). Immune cells that suppress genital herpes infections identified. ScienceDaily. http://www.sciencedaily.com/releases/2013/05/130508131703.htm
Jia Zhu, Tao Peng, Christine Johnston, Khamsone Phasouk, Angela S. Kask, Alexis Klock, Lei Jin, Kurt Diem, David M. Koelle, Anna Wald, Harlan Robins, Lawrence Corey (2013). Immune surveillance by CD8αα skin-resident T cells in human herpes virus infection. Nature, DOI: 10.1038/nature12110
Beauman, J. G. Genital Herpes: a review (2005). Am Fam Physician, 15; 72(8):1527-34.
World Health Organization, WHO (2013), http://www.who.int/vaccine_research/diseases/soa_std/en/index3.html