**1. Introduction**

Periodontal disease is an inflammatory response to bacterial biofilm accumulation around teeth. This host inflammatory response is mediated mainly by neutrophils, monocytes/macrophages, and T and B lymphocytes (T and B cells). The development of the disease is characterised by a dense inflammatory infiltrate in the connective tissue, in which polymorphonuclear leukocytes and macrophages are abundant immune cells that firstly respond to the bacterial insult. When inflammation is not resolved, antigen-presenting cells (APCs) are activated by bacterial products and interact with naive T helper cells (Th0), driving their differentiation into several subsets, such as Th1, Th2, Th9, Th17, T-follicular helper (Tfh), and regulatory T cells (Treg) [1]).

Overexpression of the Th17/Treg axis is seen in disease initiation, followed by persistence of the Th17 response in periodontitis progression in a non-human primate model of periodontitis [2]. Tregs are required to keep periodontal health homeostasis, where their presence is essential to ensure a controlled response that minimises collateral tissue damage [3]. However, recent evidence suggested Th17 might not be the main source of interleukin (IL)-17A in periodontal tissues, suggesting Tregs may have a

more prominent role in the pathogenesis of the periodontal disease [4]. These findings might change our understanding of the current literature. More recently, a new cell type named mucosal-associated invariant T (MAIT) cells has been associated with autoimmune and other inflammatory diseases in humans [5] and its role in the periodontal disease pathogenesis should be taken into consideration.

B cells, on the other hand, are part of the adaptive humoral immunity specialised in secreting antibodies and cytokines, as well as presenting antigens, and have been strongly associated with periodontal homeostasis and disease [5]. A minimal presence of B cells in healthy gingiva has been reported [6,7], which might be important to avoid bone loss due to the subclinical inflammation that occurs in the clinically healthy periodontium. B cells in periodontitis patients may contribute to chronic systemic inflammation through cytokine secretion [8]. Memory B cells can induce bone loss in rheumatoid arthritis [9], which led to the hypothesis that they express RANKL and regulate alveolar bone homeostasis during periodontitis [10]. The present narrative review aims to overview the recent findings of the importance of T and B cell subsets, as well as their cytokine expression, in the pathogenesis of the periodontal disease.

### **2. T and B Lymphocytes**
