T Cell Subsets


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T helper type 1 (Th1) cells are required for host defense against intracellular viral and bacterial pathogens. The most common markers used to identify Th1 cells are IFN-gamma production and expression of the T-bet transcription factor. For more information on Th1 cells, please see our main Th1 Cell Research Topic Page.

T helper type 2 (Th2) cells are important for host defense against large extracellular pathogens and are responsible for allergic responses. Among the cytokines secreted by Th2 cells, IL-4 is the most commonly used marker for Th2 cell identification. For more information on Th2 cells, please see our main Th2 Cell Research Topic Page.

T helper type 9 (Th9) cells protect against parasitic helminth infections, but can also cause asthma symptoms and induce experimental autoimmune encephalomyelitis. IL-9 production, together with a lack of IL-4, IL-5, and IL-13 production, is most commonly used as a marker for Th9 cells. For more information on Th2 cells, please see our main Th9 Cell Research Topic Page.

T helper type 17 (Th17) cells are involved in mucosal immunity and autoimmune disorders. These cells are proinflammatory, as they can inhibit the expansion of regulatory T (Treg) cells. Th17 cells are most commonly identified by IL-17 production in both mice and humans. For more information on Th17 cells, please see our main Th17 Cell Research Topic Page.

T helper type 22 (Th22) cells are recruited to skin where they defend against microbial pathogens, but are also associated with inflammatory skin disorders. High IL-22 production, along with low IL-17 production, is utilized most commonly as a marker for Th22 cells. For more information on Th22 cells, please see our main Th22 Cell Research Topic Page.

Follicular helper T (Tfh) cells are highly involved in the regulation and development of antigen-specific B cell immunity. The most common surface markers for Tfh cell identification are CXCR5 along with ICOS and/or PD-1. For more information on Tfh cells, please see our main Tfh Cell Research Topic Page.

Regulatory T (Treg) cells comprise 5 - 10 % of total CD4+ cells. These cells are responsible for maintaining immune homeostasis via inhibition of differentiation and activity of pro-inflammatory T helper cells. FoxP3 expression is the most commonly used marker for Treg cells in mice and humans. Human Treg cells are further differentiated by low expression levels of CD127 (CD127lo). For more information on Treg cells, please see our main Treg Cell Research Topic Page.

Natural killer T (NKT) cells consist of type I cells, which express an invariant TCR alpha chain and one of a small number of TCR beta chains, and type II cells, which express a wider range of TCR alpha chains. NKT cells in mice are most commonly identified by the alpha-GalCerCD1d-tetramer and TCR-beta surface markers. Human NKT cells, however, are most commonly identified by the Va24 invariant TCR alpha chain. For more information on NKT cells, please see our main NKT Cell Research Topic Page.

Gamma delta T cells are so named because they express TCR chains encoded by the gamma and delta gene loci. These cells have roles in both innate and adaptive immune responses. The gamma delta TCR is the most commonly used marker to identify these cells. For more information on gamma delta T cells, please see our main gamma delta T Cell Research Topic Page.

CD8+ cytotoxic T lymphocytes (CTLs) are a subset of T cells that express an alpha beta T cell receptor (TCR) and are responsible for the direct killing of infected, damaged, and dysfunctional cells, including tumor cells. CD8 expression and IFN-gamma production are the most commonly used markers for CTL identification.  Additionally, Perforin and Granzyme B, which are required for CTL-mediated cell death, are commonly utilized as secondary markers. Activated CD8+ cells express XCL1, a chemokine that attracts XCR1-expressing dendritic cells and is required for maximal priming and expansion of CTLs. The population of activated CTLs is heterogeneous. The bulk of the population is comprised of short-lived effector cells (SLEC), which die off quickly after the infection has been cleared, but there is also a smaller group of memory precursor effector cells (MPEC) that contribute preferentially to the memory cell population. Expression of the T-bet transcription factor is associated with effector CTL differentiation, while Eomes transcription factor expression is associated with memory CTL precursors. It has been reported that CTLs also produce IL-10, an anti-inflammatory cytokine, at the peak of infection to prevent excessive tissue damage. Importantly, CTLs appear to be critical for cancer prevention as Perforin suppresses lymphoma in mice and mutations in Perforin are associated with lymphoma in humans.

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