Roles of T Cells

All T cells have T cell receptors, and these always remain attached to the membranes of the T cells. Moreover, T cell receptors always recognize peptide antigens presented on MHC molecules on the surface of other cells. Despite these common features, T cells perform several, quite different functions in the body. They are first divided into two populations based on whether they have CD4 molecules or CD8 molecules.

CD4+ T cells

T cells with CD4 molecules bind peptides displayed on MHC II molecules. As the previous page shows, such peptides are derived from phagocytized sources, and thus these T cells interact with only with certain special cells. These phagocytic cells are either dendritic cells (or macrophages) or B cells. Once a T cell recognizes its specific peptide antigen presented on a dendritic cell or B cell, the T cell becomes activated so that it now goes on to promote an aspect of an immune response. These activated T cells are called helper T cells, although this term does not accurately describe all of their functions.

Helper T cells develop in one of two directions, depending on the cytokine environment in which they are activated. These two types are called TH1 and TH2 cells.

The TH1 cells tend to form when there is lots of strong stimulation by the phagocytized antigen and lots of activation of the innate immune system. The TH2, by contrast, tend to form with weaker, more prolonged stimulation with less activation of innate mechanisms.

One important role that TH1 cells perform is to travel around the body to macrophages that have phagocytized the antigen. The TH1 cells bind to these cells and release INF-gamma (interferon-gamma). In the macrophage, this cytokine increases the fusion of lysosomes with phagosomes and it especially cranks up mechanisms used to kill phagocytized microbes.

This activation of macrophages by INF-gamma is important for dealing with sophisticated pathogens such as those that cause tuberculosis or leprosy. These pathogens can remain alive in macrophages after phagocytosis, and indeed, they really are intracellular parasites. They can live and reproduce inside unactivated macrophages for long periods.

Why aren't macrophages always "activated"? This probably is because the killing mechanisms of macrophages and neutrophils can damage the body as well as microbes. If activation of macrophages did not require a specific immune response, they might cause far more unnecessary damage to the body than they do. Consider that in tuberculosis the damage to the body is caused by macrophages fighting the bacteria rather than by anything the bacteria release.

A second role of helper T cells is to "help" B cells respond to antigens. Many antigens cannot by themselves cause a specific B cell to divide into a clone of antibody secreting plasma cells. In addition to binding the antigen, the B also phagocytizes some of the antigen and displays peptides on MHC II molecules. An activated helper T must bind to the cell and also release appropriate cytokines. Only when this happens, can the B cell divide into a clone.

The cytokines secreted are different for different types of helper T cells, which can be either TH1 or TH2. In the case of TH1, cells in the ensuing clone tend to undergo heavy chain switching so that they produce IgG, which is a good opsonin. With TH2, IgE tends to get made. Also, TH2 can lead to IgM or IgA, with the latter being made especially in MALT.

CD8+ T Cells

Recall that the T cell receptors on T cells with the CD8 molecule recognize antigen displayed on MHC I molecules. Thus, the role of CD8+ T cells is to identify cells that are synthesizing protein that is not a normal part of the body. This, of course, is what happens in a virally infected cell.

A CD8+ T cell begins to divide into a clone following its encounter with another cell displaying its specific peptide on an MHC I molecule. In a lymph node this initial cell is likely to be a dendritic cell. Dendritic cells not only have MHC II molecules, but have MHC I molecules too.

The cells in the clone derived from the activated CD8+ cell are termed cytotoxic T cells. These leave the lymph node and move around the body looking for ordinary cells in the body displaying the specific peptide on MHC I molecules. Since these cells are virally infected, they must undergo apoptosis so that they do not generate more viruses that go on to infect other cells.

A cytotoxic T cell, of course, recognizes a virally infected cell through the binding of its T cell receptor to the specific peptide displayed on MHC I molecules. Once this happens the T cell forms an adhesion complex with the infected cell. This is an extended area over which the membranes of the two cells are very close together. Into this tight space the cytotoxic T cell releases the contents of secretion vesicles.

The secretion vesicles contain perforin, which forms channels in the infected cell, and granzymes (and another enzyme), which move through the perforin into the cell. The granzymes are proteases that activate certain caspases, which are a set of enzymes that trigger the set of processes that take place in apoptosis. (Another secreted substance, Fas ligand, can also activate caspases via another pathway.)

Below is a figure that requires the SVG plug-in. Work down the list to see if you understand how a cytotoxic T cell acts on a virally infected cell. To begin, click on the figure so it pays attention to your mouse.