Effector T-Helper Cell Subtypes

EFFECTOR T-HELPER CELL SUBTYPES

Following maturation in the thymus, mature but naive CD4+ helper T-cells access the systemic blood and lymphatic circulations. In this naive state they have yet to be stimulated by antigen. The antigen-driven activation signals involve initially TCR interactions with MHC presented peptide and subsequent CD3 activation. This is followed by the interaction of a variety of costimulatory molecules on the surface of the APC (e.g. CD80, CD86) with surface receptors (e.g. CD28) on the helper T-cell. Once the helper T-cell is activated it can proliferate in an autocrine or paracrine fashion driven by secreted IL-2. These proliferating helper T-cells will then differentiate depending on their cytokine environment; for example, IFN-γ and IL-12 drive the differentiation to a T_H1 subpopulation of cells while IL-4 drives the differentiation to a T_H2 subpopulation of cells.

Apart from IL-2 the main cytokines produced by T_H1 cells are IFNγ and TNFβ, and the main cell partner for T_H1 cells are the APCs. The T_H1 cells classically promote cell-mediated immune responses maximizing the effectiveness of APCs and the proliferation of cytotoxic CD8+ T-cells. Apart from IL-2 the main cytokines produced by T_H2 cells are IL-4, 5,6,10 and 13, while the main cell partner for T_H2 cells is the B-cell. The T_H2 cells classically promote the humoral immune responses stimulating B-cells to proliferate to undergo Ig class switching and increase Ig production and secretion.

The above model of helper T-cell subpopulations and how various cytokines can serve to promote the differentiation pathway to either T_H1 or T_H2 phenotype is recognized to be an oversimplification. However, the basic model serves to emphasize that distinct populations of helper T-cells exist that fulfil many different and varied functions.