As mentioned previously, CD4 is a marker for Th cells. CD4 recognizes MHC II molecules presenting antigens, usually by professional antigen-presenting cells. A complex set of interactions determines how the Th cell will respond once it acknowledges its antigen. This often depends on cytokine release by macrophages or other cells during the innate response; different pathogens will elicit different cytokine responses. Scores of various cytokines can also act in concert with each other. Examples of cytokines are: IL-1, IL-2, IL-6, TNF-α, IFN ϒ, etc. Table 8 summarizes some cytokines, what type of T helper cell evolves, and how that particular T helper cell will function.
Table 8. Activation and Function of T Helper Cells. | Th 1 cells | Th 2 cells | Th 17 cells | Tfh cells* | T reg cells** |
| Cytokines that induce differentiation | IL-2 IFN- | IL-4 | IL-6 IL-21 | IL-16 TGF- IL-23 | TGF-B |
| Characteristic cytokines that the Th cell secretes | IL-2 IFN- | IL-4 IL-5 | IL-17 IL-6 | IL-21 | TGF-B IL-10 |
| Function | Activates macrophages | Activates cellular and antibody response to parasites | Enhances neutrophil response | Activates B cells; maturation of antibody response | Suppresses other effector cells |
*Tfh = T follicular helper
**T reg = T regulatory
As you can see, there is great interdependence between innate and adaptive immune responses. In addition, the type of Th response will often determine the course of the host's disease. A classic example is Mycobacterium leprosae infection. If the T cells respond as Th-1 cells, a form of leprosy will develop, known as "tuberculoid," in which the infection is contained and does not spread or do tissue damage. If, however, a Th-2 response occurs, "lepromatous" leprosy develops, which is invasive and damaging to the tissues. This oversimplifies but shows how vital the cytokine and Th responses can be.
To summarize T helper cell activation and function, the following occurs:
1. In the lymph node, an MHC II molecule on an antigen-presenting cell presents antigen to a Th cell.
2. The TCR on the Th cell recognizes and attaches to antigen, and the CD4 co-receptor recognizes the MHC II molecule.
3. Other co-receptors are also engaged (the entire process is beyond the scope of this course).
4. A signal is sent to the nucleus to begin replicating its DNA, and the cell rapidly divides into many daughter cells (a process known as "cloning").
5. As indicated in the chart above, The Th cells also have cytokine receptors on their membrane and will respond accordingly to form the Th effector cells.
6. Some daughter cells (clones) form memory cells. These cells do not act as effector cells but remain for an extended period and respond quickly to secondary infection.
