T lymphocyte family at a glance

T lymphocytes constitute the most important cells of the immune system. The ”T” stands for the thymus, where these cells are developed in. The vast majority of these cells express T cell receptor (TCR) molecules, which are required for recognition of antigenic peptides presented by the major histocompatibility complex (MHC) molecules expressed on different cell types. Recognition of antigens is followed by activation and proliferation of these cells, which is required for different types of immune responses. Below, different groups of T cells are described.

CD8+ T cells
These cells are also called cytotoxic T cells (CTL), and are characterized by expression of CD8 molecules. CTL recognize their targets by binding to antigenic peptide presented by MHC-I molecules expressed by almost all cells. CTL can recognize and destroy virally infected cells and tumor cells by inducing apoptosis in these cells. This is done by releasing the cytotoxic molecules such as perforin and granzymes. Perforin forms pores in the target cell's membrane. This is followed by activation of caspases by granzymes, which leads to  cell death by a programed cell death (apoptosis). CTL are also involved in graft rejection.

CD4+ T cells
These cells constitute a big group of T cells, which play a central and key role in the immune responses. CD4+ T cells recognize their targets by binding to antigenic peptides presented by MHC-II molecules expressed by antigen presenting cells sush as macrophages or dendritic cells.

Naive CD4+ T cells can differentiate into 4 distinct T cell populations including T helper 1 (Th1), Th2, regulatory T cells (Treg) and Th17 cells depending on what kind of cytokines or growth factors are present in cells' environment. The presence of interleukin (IL)-12 skews towards Th1, IL-4 towards Th2, transforming growth factor beta (TGF beta)  towards Treg and finally a combination of IL-6 and TGF-beta stimulates differentiastion of naive CD4+  T cells towards Th17 cells. The differentiated cells are characterized by expression of different transcription factors such as T-bet, GATA-3, FoxP3 and  RORγ for Th1, Th2, Tregs and Th17 cells respectively.

CD4+ T cells have different characteristics and are involved in different types of immune responses. Th1 cells secret IFN gamma and TNF beta and are mainly involved in cellular immune responses via stimulating macrophages, dendritic cells and CD8+ cytotoxic T cells. They can also stimulate B cells to generate antibodies involved in the antibody-dependent cell-mediated cytotoxicity. Th2 cells produce IL-4, IL-5,.IL-10, IL-13 and are mainly involved in humoral immune response via stimulating B cells to proliferate and generate antibodies. Interestingly, Th1 and Th2 cells can regulate each others differentiation or activation. For example, Th1-derived IFN gamma prevents IL-4 production. On the other hand, Th2-derived IL-10 can prevent IFN gamma  and L-12 production. Treg cells secert IL-10 and TGF beta, and are known to play a suppressive or regulatory roles in immune responses. Absence of these cells has been reported to be associated with the development of autoimmunity. Unlike Treg cells, which have anti-inflammatory properties, the Th17 cells are involved in induction of local inflammation and autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, allergic reactions and in mediating allograft rejection via secretion of proinflammatory cytokines IL-21, IL-22 and IL-17, which may further stimulate secretion of other proinflammatory cytokines.

Natural killer T (NKT) cells 
NKT cells are small group of T cells, which co-express some of the NK cells' and T cells' markers such as CD16 and TCR. After activation, they can produce cytokines or cytolytic molecules. Thus, they have both T cell and NK cell activities as well. These cells normally recognize glycolipid antigens presented by CD1d molecules. They are also able to recognize and eliminate some tumor cells and cells infected with some viruses. They can also be involved in autoimmunity, allergic inflammation or transplant immunity.

γδ T cells
These cells are present mainly within the intraepithelial lymphocytes in the gut. The nature of antigens and the mechanism by which these cells recognize them is not fully understood. However, unlike the majority of T cells, the γδ T cells are not MHC restricted. They have also been shown to have some phagocytic activities. These cells can apparently participate in both innate and adaptive immune responses.