*2.1. T Lymphocytes*

T lymphocytes (T cells) are immune cells involved in host defence and control of immune-mediated inflammatory disease development. They can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface. Most T cells are composed of two glycoprotein chains named α (alpha) and β (beta) TCR chains. However, a smaller group of T cells, named γδ T cells, presents a gamma/delta composition. They are an important subset of T cells as they can recognise a broad range of antigens without the presence of major histocompatibility complex (MHC) molecules [11]. T cells are subdivided into Th, Treg, T cytotoxic (CD8+), natural killer, and memory cells. Also, T cell anergy has been defined as a mechanism of peripheral tolerance that determines the functional inactivation of T cells following antigen recognition under non-optimal conditions [12].

Naive CD4+ T cells are activated after interaction with antigen-MHC complex and di fferentiate into specific subtypes depending on the cytokine microenvironment [13]. After such interactions, they become activated and di fferentiated into e ffector T cells, which are responsible for the production of e ffector molecules, such as pro-/anti-inflammatory cytokines and cytotoxic molecules. Most of the effector T cells undergo programmed cell death after the antigen clearance. The ones that survive di fferentiate into memory T cells. Th cells are classified as Th1, Th2, Th17, and Treg subpopulations based on their unique cytokine properties [14].

Besides the classical Th cell subpopulations, Tfh, Th9, and Th22 cells have recently been defined as new subpopulations that produce IL-21, IL-9, and IL-22, respectively [14,15]. Tfh is a specialised CD4+ T-cell subset that provides survival, proliferation, and selection signals by engaging in cognate interactions with B cells [16]. Th9 cells have been shown to present both beneficial and detrimental functions. Among the beneficial functions is their ability to initiate antitumor immunity and immune response to helminth parasites [17]. Detrimental functions of Th9 cells include the promotion of allergic inflammation and the mediation of some types of autoimmunity [17]. Duhen et al. [18] showed that memory T cells with skin-homing properties from healthy donors are characterised by the production of IL-22 in the absence of IL-17 and IFN-γ. The authors found that several T cell clones isolated from psoriatic lesions were Th22. Their function is the specific production of IL-22, which has been linked to skin homeostasis and inflammation [14].

Cytotoxic T lymphocytes (CD8+ T cells) are generated in the thymus and express a dimeric co-receptor, usually composed of one CD8 α and one CD8β chain, and they recognise peptides presented by MHC class I molecules. CD8+ T cells present three major mechanisms to kill infected or malignant cells: (a) secretion of cytokines, primarily TNFα and IFN-γ, which have anti-tumor, anti-viral, and anti-microbial e ffects, (b) production and release of cytotoxic granules (also found in NK cells), which contain two families of proteins, perforin and granzymes, and (c) destruction of infected cells via Fas/FasL interactions which can result in apoptosis of the target cell. Besides cytotoxic activities, CD8+ T cells also have regulatory/suppressor functions (CD8+ Treg), since they can control other leukocytes to avoid excessive immune activation and its pathological consequences [19].

Besides the T cells subgroups mentioned above, mucosal-associated invariant T (MAIT) cells represent a unique subset of innate-like T cells described in the late 1990s [20]. MAIT cells represent the most abundant innate-like T-cell population within human beings, comprising up to ~5% of the total T-cell population [21]. Characterisation of the MAIT cells in the buccal mucosa showed that the major subset displayed a tissue-resident and activated profile with high expression of CD69, CD103, HLA-DR, and PD-1. These tissue-resident MAIT cells produced higher IL-17 levels than tissue non-resident and circulating populations [22]. New research projects should be stimulated to better understanding the role of tissue-resident MAIT cells in the osteoclastogenesis activation in periodontal diseases.
