T-cells originate from haematopoietic stem cells in the bone marrow and migrate to the thymus to undergo maturation. The T-cell precursor rearranges its T-cell receptor genes in the thymus. Immature T-cells that recognise self MHC then receive a signal for survival and cells that interact with cell antigens are swiftly removed and destroyed, this process is known as positive and negative selection in the thymus. Mature T-cells are then able to encounter foreign antigens presented by MHC molecules in the peripheral lymphoid organs where the cells are then activated and can proliferate and destroy the organism.
Naive T cells need three signals for activation:
- Naive T cell receives a signal from TCR contacting MHC/peptide on APC (signal 1): involved CD3 and zeta
- Professional APC also express co-stimulatory molecules (B7.1/2) that bind CD28 expressed by naive T cells delivers signal 2 to the cell
- APC also release cytokines which bind cytokine receptors now-upregulated on naive T cells which deliver a signal
If a T cell doesn't receive all 3 of these signals, the T cell can enter a state of energy where it is unresponsive - even if it is restimulated with all of the needed signals. This can leas to peripheral tolerance.
There are 2 classes of T-cells CD8+ and CD4+.
CD8+ also known as cytotoxic T cells recognise MHC class 1 molecule, in order prevent viral pathogens evading the immune system by avoiding interaction with CD8+ cells can be involved in cross presentation.
There is a subset of CD4+ T cells known a Treg that suppress immune responses. This is crucial for tolerance and suppressing autoimmune responses. A deficiency of Treg can result in a severe autoimmune syndrome, IPEX.
CD4+ cells, also known as help T cells, function by secreting cytokines which result in effects in other cell types. CD4+ cell recognises MHC class II.