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Activated helper T cells can differentiate into one of four distinct subtypes, summarized in [link] . The differentiation process is directed by APC-secreted cytokines . Depending on which APC-secreted cytokines interact with an activated helper T cell, the cell may differentiate into a T helper 1 (T H 1) cell, a T helper 2 (T H 2) cell, or a memory helper T cell. The two types of helper T cells are relatively short-lived effector cells , meaning that they perform various functions of the immediate immune response. In contrast, memory helper T cells are relatively long lived; they are programmed to “remember” a specific antigen or epitope in order to mount a rapid, strong, secondary response to subsequent exposures.
T H 1 cells secrete their own cytokines that are involved in stimulating and orchestrating other cells involved in adaptive and innate immunity. For example, they stimulate cytotoxic T cells, enhancing their killing of infected cells and promoting differentiation into memory cytotoxic T cells . T H 1 cells also stimulate macrophages and neutrophils to become more effective in their killing of intracellular bacteria. They can also stimulate NK cells to become more effective at killing target cells.
T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production . Various cytokines produced by T H 2 cells orchestrate antibody class switching , which allows B cells to switch between the production of IgM, IgG, IgA, and IgE as needed to carry out specific antibody functions and to provide pathogen-specific humoral immune responses.
A third subtype of helper T cells called T H 17 cells was discovered through observations that immunity to some infections is not associated with T H 1 or T H 2 cells. T H 17 cells and the cytokines they produce appear to be specifically responsible for the body’s defense against chronic mucocutaneous infections. Patients who lack sufficient T H 17 cells in the mucosa (e.g., HIV patients) may be more susceptible to bacteremia and gastrointestinal infections. Blaschitz C., Raffatellu M. “Th17 cytokines and the gut mucosal barrier.” J Clin Immunol. 2010 Mar; 30(2):196-203. doi: 10.1007/s10875-010-9368-7.
| Subtypes of Helper T Cells | |
|---|---|
| Subtype | Functions |
| T H 1 cells | Stimulate cytotoxic T cells and produce memory cytotoxic T cells |
| Stimulate macrophages and neutrophils (PMNs) for more effective intracellular killing of pathogens | |
| Stimulate NK cells to kill more effectively | |
| T H 2 cells | Stimulate B cell activation and differentiation into plasma cells and memory B cells |
| Direct antibody class switching in B cells | |
| T H 17 cells | Stimulate immunity to specific infections such as chronic mucocutaneous infections |
| Memory helper T cells | “Remember” a specific pathogen and mount a strong, rapid secondary response upon re-exposure |
Cytotoxic T cells (also referred to as cytotoxic T lymphocytes , or CTLs) are activated by APCs in a three-step process similar to that of helper T cells. The key difference is that the activation of cytotoxic T cells involves recognition of an antigen presented with MHC I (as opposed to MHC II) and interaction of CD8 (as opposed to CD4) with the receptor complex. After the successful co-recognition of foreign epitope and self-antigen, the production of cytokines by the APC and the cytotoxic T cell activate clonal proliferation and differentiation. Activated cytotoxic T cells can differentiate into effector cytotoxic T cells that target pathogens for destruction or memory cells that are ready to respond to subsequent exposures.
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