T helper cell

The T helper cells (T_h cells) are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.

Mature T_h cells express the surface protein CD4 and are referred to as CD4⁺ T cells. Such CD4⁺ T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4⁺ cell will aid those cells through a combination of cell to cell interactions (e.g. CD40 and CD40L) and through cytokines. Nevertheless, there are rare exceptions; for example, sub-groups of regulatory T cells, natural killer cells, and cytotoxic T cells express CD4. All of the latter CD4⁺ T cell groups are not considered T helper cells.

T helper 17 cell

T helper 17 cells (T_h17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that encourage Th17 differentiation discourage Treg differentiation. However, T_h17s are developmentally distinct from T_h1 and T_h2 lineages. T_h17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces, but they have also been implicated in autoimmune and inflammatory disorders. The loss of T_h17 cell populations at mucosal surfaces has been linked to chronic inflammation and microbial translocation.

Differentiation

Transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) contribute to T_h17 formation in mice and humans. Key factors in the differentiation of T_h17 cells are, besides others, the signal transducer and the activator of transcription 3 (Stat3) and the retinoic acid receptor-related orphan receptors gamma (RORγ) and alpha (RORα). The T_h17 cells can alter their differentiation program ultimately giving rise to either protective or pro-inflammatory pathogenic cells. The protective and non-pathogenic T_h17 cells induced by IL-6 and TGF-β are termed as Treg17 cells. The pathogenic T_h17 cells are induced by IL-23 and IL-1β. IL-21, produced by T_h17 cells themselves, has also been shown to initiate an alternative route for the activation of T_h17 populations. Both interferon gamma (IFNγ) and IL-4, the main stimulators of T_h1 and T_h2 differentiation, respectively, have been shown to inhibit T_h17 differentiation.