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.