T Cell Development and Proliferation
TCRs become expressed following gene rearrangement, producing double positive (CD4+, CD8+ cells). Mature cells, either CD4+ or CD8+, develop in the thymus. It is unclear how this choice is made, although it is possible that MHC I or II recognition is an important part of this .
Negative selection also occurs in order to prevent self-reactivity.
Unlike B cells, which can recognize antigen alone, TCR can recognize antigen only when presented in an MHC class II molecule.
T Cell Proliferation
Both Th and Tc cells become activated following presentation of antigen on MHC Class II receptors on APCs.
Th cells become activated following ligation of TCR and CD3.
This causes a cascade of biochemical events that eventually results in growth and proliferation, primarily through the activity of IL-2.
Antigen activation causes CTL-Ps to begin expressing both Interleukin-2 and the IL-2 Receptor. Autocrine activation of IL-2R induces proliferation.
In some cases, the amount of IL-2 may be sufficient to induce proliferation, and this is especially true for memory CTL-Ps, which have lower activation requirements than do naive cells.
Inhibition of Proliferation
T cell proliferation during alloantigenic response to transplanted tissues is a serious concern. Mitotic inhibitors such as azathioprine, cyclophosphamide, or methotrexate are sometimes given to lessen the immune response by preventing T cell proliferation.
However, these mitotic inhibitors are non-specific and cause potentially serious systemic effects.
In Vitro T Cell Proliferation Assays
T cell proliferation may be induced in vitro by plant lectins, including phytohemagglutinin (red kidney beans), concavalin A (Jack beans), or pokeweed. These mitogenic factors act through JAK/STAT pathways.
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