# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 5 Role of Langerhans Cells in Oral Lichen Planus Pathogenesis
It is concluded that LCs act as immune mediator cells and vectors of infected and phagocytic cells. Comparing the presence of Langerhans cells (LCs; CD1a), T cells (CD3), and B cells (CD20) in inflammatory processes in the cases of OLP and oral leukoplakia (OL), a noticeably elevated number of CD3+ and CD20+ cells in the submuc of OLP compared to OL (\(p<0.01\)) was stated. In the epithelium of OLP, the number of CD3+ cells was noticeably higher than in OL (\(p<0.05\)). In OLP, there was evidence of immune activation involving both T cells and B cells [85]. Characterization of EBV and Its Potential Action as Exogenous and Endogenous Antigens in the Pathogenesis of OLP  
Epstein-Barr virus (EBV), also known as Human herpesvirus 4 (HHV-4), is a member of the Herpesviridae family and the subfamily Gammaherpesvirinae, genus Lymphocytovirus. EBV is a widely distributed double-stranded DNS virus [86]. Primary infection is asymptomatic or mildly symptomatic and usually happens in childhood [87]. It can cause infectious mononucleosis, oral hairy leukoplakia, and various non-epithelial and epithelial tumors, among which the most known are [PERSON]'s lymphoma, [PERSON] lymphoma, nasopharyngeal carcinoma, and gastric cancer in adults and adolescents [88; 89]. EBV primary infects B cells and epithelial cells, but under certain conditions, it can also affect monocytes, Langerhans cells, NK and T lymphocytes, and smooth muscle cells and induce oncogenesis in all these cell types [90; 91]. There are two genotypes of EBV: EBV is classified into two types, EBV-1 and EBV-2, which differ in their DNA sequences of several genes and their oncogenic potential [92]. Between individuals, EBV is transmitted by saliva, and before infecting B lymphocytes, the virus must first cross the tonsillar epithelium [87]. There is a possible variant when the virus infects only the epithelium [93]. The prevalence of latent EBV infection among adults worldwide is more than 90%, and after primary infection, the virus persists throughout life in memory B lymphocytes [89]. B lymphocytes and oral squamous epithelial cells are the typical sites where EBV can replicate. Reactivation of the latent phase of EBV can lead to productive infection, resulting in the release of infectious EBV particles in saliva [89]. Studies have shown that stratified epithelia can be infected only from the apical surface and not from the basal surface. They are not found in the lower basal and parabasal layers. It is stated that the basal epithelial cells consistently proved resistant to infection [94; 95]. To infect oral epithelium, the fusion of the EBV envelope with the cell membrane and transport of the virus into the cell are required, which are ensured by cell surface receptors, integrins, and mediating cell-extracellular matrix and cell-cell adhesion. It is provided by the direct interaction of EBV glycoproteins gH/gL with integrins av-6 and av-8 on epithelial cells [96] and the transmembrane glycoprotein BMRF2 interaction with integrins 1 and \(\alpha\)5 [94]. In addition, [PERSON] et al. [94] showed that BMRF2 is being transported to the basolateral membranes of polarized oral epithelial cells, localized by \(\beta\)1 integrin. Such abundant BMRF-2 accumulation was observed in the epithelium of patients with oral hairy leukoplakia (OHL). It was also stated that epithelial av\(\beta\)6 integrin of oral mucosa plays an important role as a mediator of stem cell quiescence and immune surveillance through activation of TGF-\(\beta\)[97]. The virus released by stratified epithelium is highly infectious to B cells but not to epithelial tissue. To infect B lymphocytes, the EBV glycoprotein complex gH/gL/gp42 is required, as is the binding of glycoproteins gp350/220 to the cell surface receptor CR2-type 2 complement receptor (CD21) [19; 98]. This mechanism ensures EBV's continuous movement between B lymphocytes and epithelial cells, thus maintaining the persistence of the infection process.