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T cells are a type of white blood cell or lymphocyte that recognizes and targets pathogen-infected cells, or cancer cells, for clearance. T cells originate from hematopoietic stem cells in the bone marrow and precursors are shuttled to the thymus for final maturation. T cells are selective, so that they are tolerant to the body’s own cells (self-molecules) but remain highly sensitive to non-self pathogens. There are many subsets of T cells, each with important functions relating to the immune system. Immunophenotyping offers a way to identify and quantify the different populations of T cells within a sample, using antibodies to detect specific antigens expressed by these cells, which are known as markers.
Three subtypes that are commonly studied in T cell research include:
Killer T cells recognize antigens, released by the infecting agent that becomes bound to the host cell. Killer T cells are capable of identifying and interacting with diverse cell types and pathogens. The T cell receptor binds the foreign antigen triggering the release of cytotoxins into the infected cell leading to cell death.
Helper T cells facilitate the immune system in fighting infection. Th cells recognize and bind to a pathogenic antigen, leading to the release of soluble factors (cytokines) that signal to the rest of the immune system to launch a response. Th cells are classified into different subsets, including Th1 cells and Th2 cells. Th1 cells bind to phagocytic macrophages and dendritic cells. Th2 cells bind and activate B cells, required for antibody production and, thus, securing life-long immunity against certain bacterial or viral infections.
Regulatory T cells keep the immune system in check. They ensure that once an immune response has occurred it is shut down. This regulatory mechanism represses immune activity thus preventing an exaggerated immune response. Normally functioning Treg cells are critical for safeguarding against autoimmune disease.
The table below describes further classes of T cell and markers applicable to their study.
Cell | Function | Markers |
Naïve T cell | Successfully differentiated and undergone central selection in the thymus. | CD3, CD62L, CD197 |
Killer CD8 T cell | See above | CD8, IFNγ, TNFα, EOMES |
Helper CD4 T cell | See above | CD4, CD183, IFNγ, IL-2, IL-4, IL-12, IL-18, STAT4, STAT1, CD194 |
Th1 T cell | Assist in activating macrophages to combat pathogens and subvert their microbial avoidance strategies | CD3, CD4, CD28, CD4, CD45, IFNγ, TNFα, T-bet |
Th2 T cell | Produce cytokines, capable of mediating strong antibody production, eosinophil activation, and the restraint of a few macrophage capacities, giving phagocyte-independent defensive reactions. | CD3, CD4, CD45, CD184, CD365, GATA3, IL-4 |
Th17 T cell | Involved in host defense against extracellular pathogens, especially at the mucosal and epithelial borders. Dysregulation has been strongly associated with the pathogenesis of various autoimmune diseases. | CD3, CD4, CD194, IL17A, TGFβ, IL-6 |
Follicular helper T cell | A specialized subset of CD4+ T cells that help B cells produce antibodies against foreign pathogens. Found in secondary lymphoid organs (SLOs), tonsil, spleen and lymph nodes. | CD3, CD4, CD185, CD183, IL-21 |
Regulatory T cell | See above | CD4, CD25, CD127, CD152, TGFβ, IL-10, IL-12, FoxP3, STAT5 |
Central memory T cells | Provide central immunosurveillance by draining peripheral tissue sites. They provide effective long-term protection and have a high proliferative potential. Interchange into effector memory T cells upon antigen reencounter. | CD3, CD62L, CD197 |
Effector memory T cell | Present in the blood and peripheral organs for immunosurveillance in the defense against pathogens. | CD45, CD44 |
CD3 is involved in activating cytotoxic T-cells and T-helper cells.
Initiates the early phase of T-cell activation. May function as an important mediator of indirect neuronal damage in infectious and immune-mediated CNS diseases.
T cell signaling; cytotoxic T cell-antigen interactions.
Interleukin-2 receptor subunit alpha, IL2RA, TAC antigen, TCGFR
Receptor for IL2 in complex with CD122 and CD132.
TP44
Costimulation of T-cells. Induces T-cell activation and survival, interleukin-2 production, T-helper type 2 cell development and clonal expansion.
Epican, HUTCH-I, LHR, PGP-1, ECMR-III, IN, INLU, MC56, MDU2, MIC4, MUTCH-1
Leukocyte rolling, homing and aggregation. Adhesion of leukocytes to endothelial cells, stromal cells, and the extracellular matrix. Important in epithelial cell adhesion (cell-cell and cell-matrix) to hyaluronate in basement membranes and maintaining the polar orientation of cells.
Leukocyte common antigen, L-CA, PTPRC
Critical for B- and T-cell receptor-mediated activation. Also required for thymic selection.
L-selectin, SELL, LAM1, LECAM1, LYAM1, Leu-8
Leukocyte rolling and homing on activated endothelium.
IL7R
Receptor for IL7. Involved with T-cell homeostasis and function.
CTLA-4
Negative regulation of T-cell activation. Contributes to the maintenance of peripheral T-cell tolerance to self antigens. It exerts its major effects on T-cell immune responses via regulation of the cell cycle.
CXCR3, GPR9, MigR
Receptor for CXCL9, CXCL10 and CXCL11. Upon ligand binding, induces responses that are involved in leukocyte traffic, integrin activation, cytoskeletal changes and chemotactic migration.
CXCR4, HM89, LESTR, WHIM
Involved in AKT signaling cascade, regulates cell migration, hematopoietic progenitor cell homing and acts as co-receptor with CD4 for HIV-1 cell entry. Receptor for CXCL12.
CXCR5, BLR1, MDR15
Binds B-cell chemoattractant BL. Involved in B-cell migration into B-cell follicles of spleen and Peyer patches.
CCR4
Receptor for MIP-1, RANTES, TARC, and MCP-1 to regulate cell trafficking of leukocytes. Co-receptor for HIV-2.
CCR7, BLR2, CMKBR7
Activates B- and T- lymphocytes, controls migration of B-cells and memory T-cells to inflamed tissues, stimulates dendritic cell migration.
HAVCR1, TIM-1
Receptor for hepatitis A virus and TiMD4. May be involved in the moderation of asthma and allergic diseases.
Interferon gamma
Tbr2
Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays an essential role in maintaining mucosal homeostasis and preventing pro-inflammatory responses. Loss-of-function mutations in genes encoding IL-10 cytokine and IL-10 receptor have been linked to very early-onset IBD.
Transcription factor found in helper Th1 cells.
Transcription factor found in helper Th1 cells.
Transcription factor.
Tbx21
Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types, including immune cells. TGF-β signaling regulates mucosal immune system reactions and is shown to be impaired in the intestines of patients with IBD.
Transcription factor.
Neurath, M. F. Cytokines in inflammatory bowel disease Nature Rev Immunol 5 (14),329-342 (2014)