T Cells

1.         Origin of Lymphocytes

a.            Embryonic development: blood cell precursors originate mainly in the fetal liver and yolk sac.

b.            Postnatal life: the stem cells reside in the bone marrow.

c.         Stem cells differentiate into cells of the erythroid, myeloid or lymphoid series.

d.         The lymphoid series evolve into 2 main lymphocyte populations: T and B cells.

e.         The ratio of T to B cells is 3:1.

2.            Maturation of T cells

a.         T cells precursors differentiate into immunocompetent T cells within the thymus.

b.         Stem cells lack antigen receptors and CD3, CD4, and CD8 molecules on their surface, but during passage through the thymus they differentiate into T cells that can express these glycoproteins.

c.         The stem cells first differentiate to express both CD4 and CD8 (cortex) and then proceed to express either one (medulla).

d.            Development of T cells:

i.            thymocyte progenitors enter the thymus in the subcapsular region.

ii.          at this stage they express neither the antigen receptor or either of the two co-recpetors CD4 and CD8 and are known as double-negative cells.

iii.         as double-negative cells, they proliferate and express the CD3, CD4 and CD8 receptors and are known as double-positive cells.

iv.         these cells are found in the thymic cortex where they undergo positive selection and negative selection.

3.            Preprocessing of T lymphocytes

a.         The T lymphocytes, after their origination in the bone marrow, first migrate to the thymus gland.

b.         Here they divide rapidly and at the same time develop extreme diversity for reacting against different specific antigens – one of the thymic lymphocytes develop extreme diversity for reacting against different specific antigens.

c.         These different types of processed T lymphocytes now leave the thymus and spread throughout the body to lodge in lymphoid tissue everywhere.

d.         Positive Selection:

i.          only T cells specific for peptides bound to self MHC proteins mature in the thymus.

ii.          this process is mediated exclusively by thymic epithelial cells.

iii.         positive selection ensures that all mature T cells are able to respond to foreign peptides presented by self MHC molecules on antigen-presenting cells.

e.            Negative Selection:

i.          the thymus also ensure that any T lymphocytes leaving the thymus will not react against proteins or other antigens that are present in the body’s own tissues.

ii.          this process is mediated largely by dendritic cells and macrophages.

iii.         clonal deletion: CD4-positive, CD8-positive cells bearing antigen receptors for ‘self’ proteins are killed by apoptosis.

iv.            negative selection: the removal of these self-reactive cells results in tolerance to our own proteins.

4.            Functions of different types of T cells

a.         T cells perform several important functions which are divided into 2 main categories: regulator and effector.

b.         The regulatory functions are mediated primarily by helper (CD4-positive) T cells, which produce interleukins.

c.         The effector functions are carried out primarily by cytotoxic (CD8-positive) T cells, which kills virus-infected cells, tumor cells, and allografts.

5.            Categories of T cells: CD4 and CD8

a.         Within the thymus, T cells progenitors differentiate under the influence of thymic hormones (thymosins and thymopoietins) into T cell subpopulations.

b.         These cells are characterized by certain surface glycoproteins – CD3, CD4 and CD8.

c.         CD3 proteins:

i.          All T cells have CD3 proteins on their surface in association with antigen receptors.

ii.          The CD3 complex of 5 transmembrane proteins is involved in transmitting, from the outside of the cell to the inside, the information that the antigen receptor is occupied.

d.         T cells are subdivided into 2 major categories on the basis of whether they have CD4 or CD8 proteins on their surface.

e.         Mature T cells have either CD4 or CD8 proteins but not both.

6.            Functions of CD4 Lymphocytes

a.         They perform the following helper functions:

i.          they help B cells develop into antibody-producing plasma cells

ii.          they help CD8 T cells to become activated cytotoxic T cells

iii.         they help macrophages effect delayed hypersensitivity (e.g. limit infection by Mycobacterium tuberculosis)

b.         These functions are performed by 2 subpopulations of CD4 cells:

i.          Th-1 cells help the delayed hypersensitivity response by producing primarily IL-2 and gamma interferon.

ii.          Th-2 cells perform the B cell helper function by producing primarily IL-4 and IL-5.

c.            Regulation of T helper cell subtype:

i.          one important regulator of the balance between Th-1 and TH-2 cells is interleukin-12 (IL-12), which is produced by macrophages.

ii.          IL-12 increases the number of Th-1 cells, thereby enhancing host defenses against organisms that are controlled by a delayed hypersensitivity response.

iii.         Another important regulator is gamma interferon which inhibits the production of Th-2 cells.

d.         CD4 cells make up about 65% of peripheral T cells and predominate in the thymic medulla, tonsils and blood.

7.            Functions of CD8 Lymphocytes

a.         They perform cytotoxic functions, killing virus-infected, tumor and allograft cells.

b.         They kill by release of perforins, which destroy cell membranes, or by the induction of programmed cell death.

c.         CD8 cells predominate in the human bone marrow and gut lymphoid tissue and constitute 35% of peripheral T cells.