What are T Lymphocytes?

T Lymphocytes are the most common cells of immune system, that matures in the thymus and are responsible for cell-mediated immunity.

The letter T sands for thymus, the primary lymphoid gland that helps in their differentiation and development.

A group of cells known as “progenitor T cells”, from the pleuripotent stem cells of bone marrow migrate to thymus to become immunologically competent cells. They develop in thymus and expand their number by cell division to generate a large population of immature thymocytes and get differentiated into immunecompitent “T Lymphocytes” under the influence of thymic hormones.

Since progenitor T cells are not self renewing they are constantly supplied from bone marrow. The migration of haematopoietic stem cells to the thymus may be due to the chemotactic substances released by thymic epithelial cells.

Differentiation and maturation of T Lymphocytes reflects a change in nature and distribution of surface markers.

Since progenitor T cells do not express characteristic surface markers of T cells, the surface markers and receptors of developing T cells provide a powerful tool for studying the differentiation process.

In early developmental stages the thymocytes express neither CD4 nor CD8 surface markers, and are therefore referred as double negative (CD4~CD8_) cells.

During maturation the genes of T cell receptors get rearranged leading to a change in surface markers. At this point the alpha chain of TCR undergoes rearrangement. The successful rearrangement of this chain serves as a signal for these cells to undergo further proliferation.

During this time, both CD4 and CD8 start to be expressed. Thus these cells are referred to as “double positive cells (CD4+ CD8+)”. At this point the beta chain of the TCR undergoes rearrangement and the cells undergo the processes of Positive and Negative selection.

The highly variable genetic rearrangement in the Tcell receptor (TCR) genes during their development helps to generate millions of different TCRs. T cells with different TCRs, help the body’s immune system to respond to almost any protein of an invader.

Since the functional immune system requires T Lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens, the developing T cells under go the selection of T Lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens.

The Positive and Negative selection process in the thymus results in the death of about 98% of thymocytes or T cells within the thymus before their release from the thymus to reach the functional sites – peripheral/secondary lymphoid regions.

POSITIVE SELECTION:

Since TCR’s recognize antigen only in the context of MHCs, T cells must be tuned to recognize host MHC first.

During positive selection double positive T cells that can recognize self MHCs are selected for proliferation and those T cells that do not recognize self MHC die via apoptosis. The cells undergoing positive selection initially express both CD4 and CD8 co receptors.

Positive selection also assures that the right TCR selection will go with the appropriate CD4 or CDH. For example, TCRs specific for MHC II need to retain CD4, and lose CD8. If the reverse occurs, they will die via apoptosis.

The thymocyte’s fate is also determined during positive selection. Double positive cells (CD4+/CDg+) that are positively selected on MHC class II molecules eventually become CD4+ cells, while cells positively selected on MHC class I molecules mature into CD8+ cells.

NEGATIVE SELECTION:

T cells that are strongly activated by self MHC plus self peptides are eliminated through negative selection in the thymus. If they escape this elimination, they may subsequently react against self antigens, and cause autoimmune disease.

The single positive cells with CD4+ or CD8+ survived after positive and negative selection, then release from thymus to reach peripheral or secondary lymphoid tissues through circulation.