A Closer Look at CD4+ T Cells

There are four defined CD4+ T cell subsets that provide a homeostatic balance between pro and anti inflammatory responses that occur in a healthy functioning immune system. The four CD4+ T cell subsets are the Th1, Th17, Treg and the Th2 subset.

Initially, naive CD4+ T cells (termed Th0) encounter processed antigen by dendritic cells through the MHC class II and T cell receptor in the T cell zone of secondary lymphoid tissues, such as the lymph nodes. Depending on the type of cytokine released by the dendritic cell upon this interaction, the Th0 CD4 cells differentiate into either Th1, Th2, Th17 or Treg phenotypes.

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Th1 Subset

th1-subsetInterleukin-12 released by the dendritic cells will cause the Th0 CD4 cells to differentiate into Th1 functional cells. These cells secrete IFN-γ which promotes pro-inflammatory responses and will mobilize the maturation of CD8+ cytotoxic T cells and stimulate NK cells.

Th17 Subset

th17-subsetWhen a combination of Transforming Growth Factor (TGF β) and IL-6 are released together by the dendritic cell, the Th0 CD4 cells to differentiate into Th17 functional cells. These cells secrete IL-17, which also induces pro-inflammatory cytokines and tips the balance towards inflammatory immune responses.

Treg Subset

treg-subsetWhen the dendritic cells only release TGF- β, the Th0 CD4 cells differentiate into T regulatory (Treg) cells. These cells secrete IL-10 and TGF- β. IL-10 antagonises pro-inflammatory immune responses by suppressing Th1 and Th17 T cell development.

Th2 Subset

th2-subsetWhen the dendritic cells release IL-4 after Th0 binding, the cells differentiate into Th2 cells. These cells secrete IL-4 and IL-10 which antagonise pro-inflammatory responses by suppressing Th1 and Th17 T cell development. Th2 T cells also provide cytokine stimulation to promote the maturation of B cells to plasma cells and the production of antibodies.

Homeostatic balance of pro- and anti-inflammatory immune responses

balance-of-pro- and-anti-inflammatory-immune-responsesIn adaptive immune responses to pathogens, there is a critical balance between pro- and anti-inflammatory immune responses. Uncontrolled pro-inflammatory immune responses can result in damage to host tissues, whereas anti-inflammatory immune responses initiated prematurely can result in survival of the pathogen, which is deleterious for the host. Th1 and Th17 CD4+ T cell subsets result in pro-inflammatory responses and Treg and Th2 CD4+ T cell subsets result in anti-inflammatory responses. It is thought that in a natural healthy immune response, there is a homeostatic balance between these subsets, resulting in the elimination of the pathogen, but also reducing the risk of tissue damage in the process. Inability to clear pathogen, or an overload of antigen, is either a result of this balance or a cause of an imbalance.

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation