The sub populations of T cells with functional difference can be identified by means of surface markers (CD markers) or antigens.
Approximately 60 – 65% of mature T cells that leave the thymus display CDn”, CD3+, CD4+ and CDS~ markers on their surface and are generally referred as CD4 cells or TH cells or T helper cells. These cells play a major role in the initiation of immunological reactions.
In the remaining cells 30-35% poses CD2+, CD3+, CD4″ and CD8+ markers and they are referred as CD8 cells or “cytotoxic T cells” or Tc cells that act as effector cells in immunological reaction.
A small group of cells express neither CD4+ nor CDh+ but express CD2+, CD3+ markers. Function of these cells is yet to be studied.
A small fraction of CD4 cells are referred as “Delayed T cells or DTH or TD cells” due to their delay in expression of their activity. They serve as non specific effectors of inflammation.
In the same way certain CD8+ cell populations help in regulation of immunological reactions and they were referred as “T suppressor cells” or Ts cells. Both Tc cells and TD cells are considered as effectors cells and they show memory response.
TH and Tg cells are considered as regulators of immunological function. CD4+, CDg+ populations are MHC restricted (Ref MHC). In contrast the CD4~ and CDg~ cells are very few in number and they are not MHC restricted.
T Helper cells or TH cells:
TH cells a distinct subset of T-cells can be identified through their expression of the CD4 co receptor. They have no cytotoxic or phagocytic activity but are vital for immune response.
They are essential in determining B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.
Since they initiate the immune response and induce activity of the other cells of immune system they were named as T helper cells. Their response is initiated by the interaction between the T-cell receptor (TCR) and peptide major histocompatibility complex class II (pMHC II).
TH cell activation leads to the induction of a number of pathways that can result in immunoglobulin class switching and antibody production, macrophage action through direct interaction and by means of the release of soluble factors.
The TH cell response delimited by two distinct pathways involves two different subtypes of TH cells- the TH1 and TH2 cells. In most cases, TH1 cells are targeted towards intracellular pathogens such as bacteria and parasites via the activation of macrophages, while TH2 cells invoke antibody production in B cells, to neutralise extra cellular pathogens and toxins.
Once activated, the TH cells divide rapidly and release cytokines to enhance or regulate immune response.
Cytotoxic T cells or Tc cells:
Cytotoxic T cells also known as Tc, Cytotoxic Tlymphocyte, T-Killer cell, cytolytic T cell, CDg+ T-cells or killer T cell are effector cells. They play a major role in cell mediated immunity, to destroy virally infected cells, tumour cells, and tissue grafts. Tc cells express CDX glycoprotein on their surface and are associated with MHC class I.
Antigen presenting cells degrade the viral proteins into peptides and present to the Tc cells as pMHC I. The affinity between CD8 and the MHC molecule helps in keeping the Tc cell and the target cell bound closely together during antigen-specific activation.
The Tc cells response in most cases is targeted towards intracellular pathogens such as viruses, bacteria and tumor related antigens that exist in the cytosol, or contiguous nuclear compartment.
Tc cells activation leads to direct killing of target cell through induction of apoptotic signals by means of the released cytotoxic granules and lymphokines.
T suppressor or Ts Cells:
T suppressor cells are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell mediated immunity at the end of an immune reaction and suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ regulatory Ts cells have been described; they are the naturally occurring Ts cells and the adaptive Tg cells.
Naturally occurring Ts cells are also known as CD4+ CD25+ FoxP3+ Ts cells. They arise in the thymus, whereas the adaptive Tg cells also known as Tr1 cells or TH3 cells. They may originate during a normal immune response. Naturally occurring Ts cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3.
Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.
Delayed T cells or TD cells: –
This cell type is not individually well characterized; on the basis of surface markers. They are probably Thl cells, functioning to produce a delayed type hypersensitivity reaction.
The quality of cytokines they secrete is different. Subsequent exposures to the antigen induce the effectors phase of TD cells. The TD cell secretions are responsible for the recruitment and activation of macrophages and other nonspecific inflammatory cells.
Generally TD cells response occurs after 24 hours of secondary contact with the antigen, hence they were known as delayed T cells or TD cells.
The naive CD4+ and CD8+ T cells leave thymus and enter the circulation as resting cells in the GO stage of the cell cycle. The naive T cells have condensed chromatin with little cytoplasm.
They circulate continuously between the blood and lymph system (once in 24 hours) till they encounter an antigen in the secondary lymphoid organs. Since 1 in 105 naive T cell can bind with the new antigen the continuous circulation of naive T cells increase the chances of interaction of appropriate T cell with the new antigen.
If the naive T cells interact with suitable antigens through antigen presenting cells, they get differentiated in to effectors T cells. The differentiation is initiated by interaction of T cells TCR, CDs (receptors) complex, with a processed antigen bound to the surface MHC class II molecules of antigen presenting cells.
Co stimulatory factor B on antigen presenting cells is necessary for activation of naive T cells. Since it is absent on their surface resting macrophages and B cells, they fail to activate naive T cells.
Some times T cells fail to respond even after interacting with the antigen. The non responsiveness of T cells after interaction with antigen MHC class II complex is known as “clonal anergy”.
This is due to the unavailability of naive T cells to undergo clonal expansion in the absence of co stimulatory signal produced by the interaction of TCR, CDs complex on TH cells with B7 on antigen presenting cells. Apart from this, the cytokines released by the antigen presenting cells also involve in the activation process.
A series of membrane and cytoplasm events take place during differentiation and proliferation. The composition of cell membrane also changes resulting in the development of new receptors such as high affinity IL-2 and gain of specific functional characters.
Antigen interaction with naive T cell provides the first activating signal and interleukin -1 (Refer interleukins) secreted by antigen presenting cell serves as second signal for T cell activation.
Within half an hour of activation a number of transcription factors were expressed by activated T cells and release various cytokines within 1 to 2 hours of activation.
A co stimulatory signal produced by the CD2K present on TH cells and B7 present on antigen presenting cells support and enhances the differentiation process of naive T cell.
Interaction of naive T cells and antigen provides the first activating signal and interleukin -1 secreted by antigen presenting cell serves as second signal in activation of naive T cells.
Activated T cells secrete various cytokines such as interleukin -2 (IL- 2), to promote differentiation of both B and T cells. Interleukin 2 (IL-2) provides an autocrine signal to induce repeated cell divisions ((2 to 3 times a day for 4-5 days) for clonal expansions.
Some of the differentiated naive T cells remain in the body as memory cells without involving in immunological activity. Unlike effector cells they have long life span and provide quick secondary response to subsequent challenge with the same antigen.
Even though memory cells are in G () phase of life cycle like naive T cells, they get activated easily by macrophages, dendrite cells, and B cells.