Helper T cells, (Th cells) are the "middlemen" of the adaptative immune system. Once
activated, they divide rapidly and secrete small proteins called sytokines, that regulate or
"help" the immune response. These cells (also called CD4+ T cells) are a target of HIV
infection; the virus infects the cell by using the CD4 protein to gain entry. The loss of Th
cells as a result of HIV infection leads to the symptoms of AIDS.
CD4+ lymphocytes, or helper T cells, are immune response mediators, and play an
important role in establishing and maximizing the capabilities of the adaptive immune
response. These cells have no cytotoxic or phagocytic activity; and cannot kill infected
cells or clear pathogens, but, in essence "manage" the immune response, by directing
other cells to perform these tasks.
Helper T cells express T-cell receptors (TCR) that recognize antigen bound to Class II
MHC molecules. The activation of a naive helper T-cell causes it to release cytokines,
which influences the activity of many cell types, including the APC that activated it.
Helper T-cells require a much milder activation stimulus than cytotoxic T-cells. Helper
T-cells can provide extra signals that "help" activate cytotoxic cells.
Th1 and Th2: helper T cell responses
Two types of effector CD4+ T helper cell responses can be induced by a professional
APC, designated Th1 and Th2, each designed to eliminate different types of pathogens.
The factors that dictate whether an infection will trigger a Th1 or Th2 type response are
not fully understood, but the response generated does play an important role in the
clearance of different pathogens.
The Th1 response is characterized by the production of Interferon gamma which activates
the batericidal activities of macrophages, and induces B-cells to make opsonizing
(coating) antibodies, and leads to "cell mediated immunity". The Th2 response is
characterized by the release of Interleukin 4, which results in the activation of B-cells to
make neutralizing (killing) antibodies, leading to "humoral immunity". Generally, Th1
responses are more effecitve against intracellular pathogens (viruses and bacteria that are
inside host cells), while Th2 responses are more effective against extracellular bacteria,
parasites and toxin. Like cytotoxic T-cells, most of the CD4+ helper cells will die upon
resolution of infection, with a few remaining as CD4+ memory cells.
HIV is able to subvert the immune system by attacking the CD4+ T cells, precisely the
cells that could drive the destruction of the virus, but also the cells that drive immunity
against all other pathogens encountered during an organisms' lifetime.
A third type of T lymphocyte, the regulatory T cell (Treg), limits and suppresses the
immune system, and may control aberrant immune responses to self-antigens; an
important mechanism in controlling the development of autoimmune diseases.
After many cell generations, the Th cell's progenitors differentiate into effector Th cells,
memory Th cells, and suppressor Th cells.
Effector Th cells secrete cytokines, proteins or peptides that stimulate or interact
with other leukocytes, including Th cells.
Memory Th cells retain the antigen affinity of the originally activated T cell, and
are used to act as later effector cells during a second immune response (e.g. if
there is re-infection of the host at a later stage).
Suppressor T cells do not promote immune function, but act to decrease it
instead. Despite their low numbers during an infection, these cells are
believed to play an important role in the self-limitation of the immune
system; they have been shown to prevent the development of various auto-
immune disease.
Terms such as "regulatory" and "suppression" have become ambiguous after the
discovery that helper CD4+ T cells are also capable of regulating (and suppressing) their
own responses outside of dedicated suppressor T cells.
One major difference with "suppressor" (or "natural regulatory") T cells is that they
always suppress the immune system, while effector T cell groups usually begin with
immune-promoting cytokines and then switch to inhibitory cytokines later in its
repertoire. The latter is a feature of Th3 cells, which transform into a suppressor subset
after its initial activation and cytokine production.
Both suppressor T cells and Th3 cells produce the cytokine transforming growth factor
beta (TGF-β) and IL-10. Both cytokines are inhibitory to helper T cells; TGF-β
suppresses the activity of most of the immune system. There is evidence to suggest that
TGF-β may not supress activated Th2 cells as effectively as naive cells, but it is not
typically considered a Th2 cytokine.
The production of IL-2 by helper T cells is also necessary for the proliferation of
activated CD8+ T cells. Without helper T cell interactions, CD8+ T cells do not
proliferate and eventually become anergic. This cross-reliance on helper T cells is
another way the immune system tries to prevent T cell-mediated auto-immune disease.
Autoimmunity is the failure of an organism to recognize its own constituent parts
(down to the sub-molecular levels) as "self", which results in an immune response
against its own cells and tissues. Any disease that results from such an aberrant
immune response is termed an autoimmune disease. Autoimmune diseases are a
result of loss of tolerance. The exact genesis of immunological tolerance is still
elusive, but several theories have been proposed since the mid-twentieth century
to explain its origin. Three hypotheses have gained widespread attention among
immunologists: among them , one that is under consideration is : the "Suppressor
population" or "Regulatory T cells " theories, wherein regulatory T-lymphocytes
(commonly CD4+FoxP3+ cells, among others) function to prevent, downregulate,
or limit autoaggressive immune responses.