T LYMPHOCYTES
• T lymphocytes derive their name from their site of maturation in the thymus. Like B lymphocytes, these cells have
• membrane receptors for antigen. Although the antigen binding T-cell receptor is structurally distinct from
immunoglobulin,
• it does share some common structural features with the immunoglobulin molecule, most notably in
• the structure of its antigen-binding site.
• Unlike the membrane- bound antibody on B cells, though, the T-cell receptor (TCR) does not recognize free
antigen. Instead the TCR recognizes only antigen that is bound to particular classes of self-molecules
• Most T cells recognize antigen only when it is bound to a self-molecule encoded by genes within the major
histocompatibility complex (MHC).
• Fundamental difference between the humoral and cell-mediated branches of the immune system is that the B cell
is capable of binding soluble antigen, whereas the T cell is restricted to binding antigen displayed on self-cells.
• To be recognized by most T cells, this antigen must be displayed together with MHC molecules on the surface of
antigen-presenting cells or on virus-infected cells, cancer cells, and grafts.
• The T-cell system has developed to eliminate these altered self-cells,which pose a threat to the normal functioning
• L'Ike B cells, T cells express distinctive membrane molécules. All T-cell subpopulations express the T-cell
receptor, a complex of polypeptides that includes CD3; and most can be distinguished by the presence of
one or the other of two membrane molecules, CD4 and CD8.
• In addition, most mature T cells express the following membrane molecules: CD28, a receptor for the co-
stimulatory B7 family of molecules present on B cells and other antigenpresenting cells CD45, a signal-
transduction molecule.
• T cells that express the membrane glycoprotein molecule CD4 are restricted to recognizing antigen
bound to class II MHC molecules, whereas T cells expressing CD8, a dimeric membrane glycoprotein,
are restricted to recognition of antigen bound to class I MHC molecules.
• Thus the expression of CD4 versus CD8 corresponds to the MHC restriction of the T cell.
• In general, expression of CD4 and of CD8 also defines two major functional subpopulations of T lymphocytes.
CD4 T cells generally Function as T helper (TH) cells and are class-II restricted; CD8 T cells generally
function as T cytotoxic (TC) cells and are class-I restricted.
• Ratio of TH to TC cells in a sample can be approximated by assaying the number of CD4 and CD8 T cells. This
ratio is approximately 2:1 in normal human peripheral blood.
• TH cells are activated by recognition of an antigen–class II MHC complex on an antigen-presenting cell. After
activation, the TH cell begins to divide and gives rise to a clone of effector cells, each specific for the same
antigen–class II MHC complex.
• These TH cells secrete various cytokines, which play a central role in the activation of B cells, T cells, and other
cells that participate in the immune response.
• Changes in the pattern of cytokines produced by TH cells can change the type of immune response that develops
among other leukocytes.
• The TH1 response produces a cytokine profile that supports inflammation and activates mainly certain T cells
and macrophages, whereas the TH2 response activates mainly B cells and immune responses that depend upon
antibodies.
• TC cells are activated when they interact with an antigen–class I MHC complex on the surface of an altered self-
cell (e.g., a virus-infected cell or a tumor cell) in the presence of appropriate cytokines.
• This activation, which results in proliferation, causes the TC cell to differentiate into an effector cell called a
cytotoxic T lymphocyte (CTL). In contrast to TH cells, most CTLs secrete few cytokines. Instead, CTLs
acquire the ability to recognize and eliminate altered self-cells.
T CELL DIFFERENTIATION
• Regulatory T cells
• As the name suggests regulatory T cells (also called Tregs) are T cells which have a role in regulating or
suppressing other cells in the immune system. Tregs control the immune response to self and foreign particles
(antigens) and help prevent autoimmune disease. Tregs produced by a normal thymus are termed ‘natural’.
• Treg formed by differentiation of naïve T cells outside the thymus, i.e. the periphery, or in cell culture are
called ‘adaptive’.
• Natural Treg are characterised as expressing both the CD4 T cell co-receptor and CD25, which is a
component of the IL-2 receptor. Treg are thus CD4+ CD25+.
• Expression of the nuclear transcription factor Forkhead box P3 (FoxP3) is the defining property which
determines natural Treg development and function.
• FoxP3 is crucial for maintaining suppression of the immune system. Naturally occurring mutations in
theFOXP3 gene can result in self-reactive lymphocytes that cause a rare but severe disease IPEX (Immune
Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked) in humans and scurfy in mice.
Tregs suppress activation, proliferation and cytokine production of CD4+ T cells and CD8+ T cells, and are thought to
suppress B cells and dendritic cells.
Tregs can produce soluble messengers which have a suppressive function, including TGF-beta, IL-
10 and adenosine.
Additional markers of natural Tregs are CD152 (CTLA-4) and GITR (glucocorticoid-induced TNF receptor),
although it should be noted that these are also expressed by other T-cell types periodically (e.g. activated T cells) so
they are not in themselves unequivocally diagnostic.
However, the role of these markers on other T cells is not clearly defined. T cells without a specialised regulatory
capacity may also compete for resources such as growth factors and MHC class II stimulation and thus have a
regulatory role via this general mechanism of competition.
• Function of Th17 cells After differentiation of naïve T cells into Th17 effector cells, they start secreting IL-17 and IL-22. IL-
17 is a unique cytokine that do not have any homologue in the body.
• IL-17 stimulates the production of chemokines, TNF, IL-1, IL-6, and granulocyte-colony stimulating factors (G-CSF) which
take part in inflammatory reactions.
• In addition, it is also involved in the production of defensins from the epithelial surface which in turn acts as a barrier for the
invading pathogens. IL-22 is a relatively new interleukin and its function is not well established. However IL-22 is known to
maintain the epithelial integrity, increase barrier function and involve in the repair activity following inflammation.
