An Overview of T Helper Cells and Their Role in the Immune System

The T helper cells ( T h cells), also known as CD4 + cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. Genetic variation in regulatory elements expressed by CD4 + cells determines susceptibility to a broad class of autoimmune diseases.

Structure and General Function

T h cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological insult (for example; virus vs. extracellular bacterium vs. intracellular bacterium vs. helminth vs. fungus vs. protist). Mature T h cells express the surface protein CD4 and are referred to as CD4 + T cells.

Effector Response and Lineage Diversity

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 displays a peptide antigen on MHC class II proteins, a CD4 + cell will aid those cells through a combination of cell to cell interactions (e.g. CD40 (protein) and CD40L) and through cytokines. T h cells are not a monolithic immunological entity because they are diverse in terms of function and their interaction with partner cells. In general, mature naive T cells are stimulated by professional antigen presenting cells to acquire an effector function. These are defined by the presence of a lineage-determining (or lineage-specifying) transcription factor (also called master regulator, though the term has been criticized for being too reductive). The loss of function in a lineage specifying transcription factor results in the absence of the corresponding class of helper T cell which can be devastating for the health of the host.

Development and Activation of Naive Helper T Cells

Following development in the thymus, these cells (termed recent thymic emigrants (RTE)) egress from the thymus and home to secondary lymphoid organs (SLO; spleen and lymph nodes). Of note, only a very small minority of T cells egresses from the thymus (estimates commonly range from 1–5% but some experts feel even this is generous). Maturation of RTE in SLO results in the generation of mature naive T cells (naïve meaning they have never been exposed to the antigen that they are programmed to respond to). After maturation, these cells exhibit specific changes:

• Naive T cells now lack or have downregulated (reduced) expression of the RTE-related surface markers, such as CD31 and PTK7.
• They show reduced expression of Complement Receptor 1 and 2 (CR1, CR2).
• There is a reduction in the production of interleukin 8 (IL-8).

T Cell Receptor (TCR) and Antigen Presentation

Like all T cells, they express the T cell receptor- CD3 complex. The T cell receptor (TCR) consists of both constant and variable regions. The variable region determines what antigen the T cell can respond to. CD4 + T cells have TCRs with an affinity for Class II MHC, and CD4 is involved in determining MHC affinity during maturation in the thymus. Class II MHC proteins are generally only found on the surface of professional antigen-presenting cells (APCs). Professional antigen-presenting cells are primarily dendritic cells, macrophages and B cells, although dendritic cells are the only cell group that expresses MHC Class II constitutively (at all times).