TCRαβ T cells, which are CD3+ cells with TCRs composed of α and β chains, predominantly mature in the thymus and then migrate mainly to lymph nodes and the spleen. These cells require antigen processing/presentation via the major histocompatibility complex in dendritic cells (DCs) to induce an inflammatory response. On the other hand, TCRγδ T cells, also CD3+ T lymphocytes, possess TCRs with γ and δ chains. They also mature in the thymus but primarily migrate to mucosal tissues like the lung, intestines, and skin. TCRγδ T cells, also known as intraepithelial lymphocytes, have a strong affinity for submucosal sites and the epithelium, serving as a primary defense for epithelial surfaces.

Unlike TCRαβ T cells, TCRγδ T cells can be activated without the involvement of antigen processing or presentation by DCs. Interestingly, TCRγδ T cells can respond to antigens through innate cellular responses, such as pathogen-associated molecular patterns (PAMPs), or occasionally through classical TCRαβ T cell responses. It remains unclear whether this responsiveness variation is due to subpopulations of TCRγδ T cells or plasticity within the same cell. These cells bridge the gap between adaptive and innate immune responses due to their unique duality. Moreover, TCRγδ cells can mount an immediate response to antigens and typically do not exhibit memory. In contrast to TCRαβ T cells' proinflammatory response, TCRγδ T cells can offer protection without inducing inflammation. They can expand in response to viral and bacterial infections and produce either proinflammatory cytokines (interleukin [IL]–17, interferon [IFN]–γ) or regulatory/suppressive cytokines (transforming growth factor β [TGFβ], lymphocyte-activation gene 3). Furthermore, TCRγδ T cells have the ability to suppress the immunoglobulin E (IgE) response to inhaled antigens, effectively preventing allergen-induced inflammation.
Most classical adaptive immune T lymphocytes are CD3+ cells with TCRs that are composed of α and β chains (TCRαβ T cells). These cells mature in the thymus and egress mostly to lymph nodes and the spleen. The classical activation of TCRαβ cells requires antigen processing/ presentation, typically via the major histocompatibility complex, in a DC, usually to induce an inflammatory response. CD3+ T lymphocytes with TCRs expressing γ and δ chains (TCRγδ T cells) also mature in the thymus, but the majority of these cells egress to mucosal tissues (i.e., lung, intestines, and skin) and represent only a minority of T cells in the peripheral blood and systemic lymphoid tissues. TCRγδ T cells, often referred to as intraepithelial lymphocytes, preferentially localize to submucosal sites and
BALT,bronchus-associatedlymphoidtissue;IFN-γ,interferonγ;IgA,IgE,IgG,andIgM,immunoglobulinsA,E,G,andM;IL-10,interleukin10;iNKT,invariantnaturalkillerT;NK,naturalkiller;TCR,Tcellreceptor;TELT,tertiaryectopiclymphoidtissue;Th1andTh2,Thelper1andThelper2.
epithelium and are considered a first line of defense of epithelial surfaces.
In contrast to TCRαβ T cells, the classical antigen activation of TCRγδ T cells does not require antigen processing or presentation by DCs. Of interest is that TCRγδ T cells have been shown to be capable of responding to antigen either in the manner of an innate cellular response, via pathogen-associated molecular patterns (PAMPs, described later in this chapter), or, in some circumstances, in the manner of a classical TCRαβ T cell response. Whether this variation in responsiveness is due to the presence of subpopulations of TCRγδ T cells or to plasticity (alterations) of the same cell is not clear. Because these cells express this unique duality, they are considered to be a link between adaptive and innate immune responses. Furthermore, TCRγδ cells can respond immediately to antigen and generally do not demonstrate memory. In contrast to the typical TCRαβ T cell proinflammatory response, TCRγδ T cells can provide protection without inducing inflammation. TCRγδ T cells have been shown to expand in response to viral and bacterial infections and synthesize either proinflammatory cytokines (interleukin [IL]–17, interferon [IFN]–γ) or regulatory/ suppressive cytokines (transforming growth factor β [TGFβ], lymphocyte-activation gene 3). TCRγδ T cells also suppress the immunoglobulin E (IgE) response to inhaled antigen, further preventing allergen-induced inflammation.