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Helper T Cells

Helper T cells are

Types of Helper T Cells

There are two distinct kinds:

Origin of Helper T Cells

Like all T cells, Th cells arise in the thymus.
Link to drawing showing the anatomy of the lymphatic system, including the location of the thymus. (52K).
The antigen-presenting cells (APCs) are called dendritic cells (DC). They

(Dendritic cells can also present intact antigen directly to B cells. In this case, the engulfed antigen is not degraded in lysosomes but is returned to the cell surface for presentation to B cells bearing BCRs of the appropriate specificity.)

There are two kinds of dendritic cell that present antigens to T cells:

Th1 Cells

Th1 cells are produced when DC1-type dendritic cells and pre-Th cells form an immunological synapse in which the dendritic cell

The paracrine stimulation by IL-12 activates (through JAK-STAT pathways) the Th1 cells to secrete their own lymphokines:

These

Th2 Cells

Th2 cells are produced when DC2-type dendritic cells present antigen to the T cell's receptor for antigen (TCR) and, presumably, one or more paracrine stimulants. The identity of the cytokine(s) is still uncertain (indicated by a ? in the figure).

The major lymphokines secreted by Th2 cells are
Link to graphic showing how Th2 cells stimulate B cells to mature into antibody-secreting plasma cells.

Two transcription factors have been found that play a critical role in the choice between becoming a Th1 or a Th2 cell.
  • T-bet for Th1 cells
  • GATA-3 for Th2 cells
T-bet produces Th1 cells by
  • turning on the genes needed for Th1 function (e.g., for IFN-γ)
  • blocking the activity of GATA-3.
Mice whose genes for T-bet have been "knocked-out" lack Th1 cells and have elevated numbers of Th2 cells (making them susceptible to such Th2-mediated disorders as asthma).

The CD8+ Cytotoxic T Cells (CTL) also come in two subsets:
  • Tc1 that, like Th1 cells, secrete IFN-γ and
  • Tc2 that, like Th2 cells, secrete IL-4.

Reciprocal inhibition of Th1 and Th2 cells.

The antigenic stimulus that sends pre-Th cells down one path or the other also sets the stage for reinforcing the response.

A Th1 response inhibits the Th2 path in two ways: A Th2 response inhibits the Th1 path:

Negative feedback of Th1 and Th2 cell formation

There is also evidence that late in the immune response, negative feedback mechanisms come into play to dampen the response.

Th1 and Th2 cells have different chemokine receptors.

Chemokines are cytokines that are chemotactic for (attract) leukocytes. Because they are chemotactic cytokines, chemokines are designated by the initials CC.

Chemokines bind to receptors on the responding leukocyte. The receptors are transmembrane proteins with the chemokine binding site exposed at the surface of the plasma membrane. Chemokine receptors are designated CCR.

With their different functions, we might expect that Th1 cells and Th2 cells would respond differently to chemokines. And so they do.

CCR3

One chemokine that binds to CCR3 is called eotaxin. It is secreted by epithelial cells and phagocytic cells in regions where allergic reactions are occurring.

CCR3 is found on all cells implicated in allergic responses (e.g., asthma).

CCR5

CCR5 is found on CCR5 also acts — along with the CD4 molecule — as a coreceptor for HIV-1, the retrovirus that causes AIDS. This fact may explain
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4 December 2005