Activation and Differentiation of T Helper cells

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Activation and Differentiation of T Helper cells

  • The principal event that biases immune reactivity towards the cellular inflammatory response is the transformation of naive Th0 cells into Th1 cell type, whereas conversion of Th0 lymphocytes into Th2 cells activates humoral response and antibody production (functional polarization of T helper cells).
  • This needs a number of specific stimulatory signals from APC to T helper cells:
  1. processing of Ag and presentation of membrane Ag-HLA complex for recognition by T helper cells;
  2. expression of costimulatory molecules upon APC membranes for additional activation of T helpers;
  3. release of a specific set of cytokines that stimulate T helper differentiation.
  • T helpers recognize complex “Ag-HLA II” by antigen-specific membrane receptor TCR. CD4 and CD3 molecules of Th cells also take part in the reaction making the recognition more stable. This delivers the first signal for T helper activation.
  • At the same time, the expression of costimulatory molecules upon the membranes of helper cells is elevated. T cells bear specific costimulatory molecule CD28 that binds to its counterpart molecules CD80 or CD86 expressed on the membrane of APC.
  • This interaction provides the second signal for activation of T helpers. Without costimulation T cell binding to processed Ags leads not to activation but to suppression and apoptosis of reactive cell clone.
  • It results in energy (cell unresponsiveness) in concern to recognized Ag. If antigen-specific B-lymphocyte serves as the antigen-presenting cell it also expresses costimulatory molecules for activation. The most essential is the CD40 receptor that reacts with specific CD40 ligand (CD40L or CD154 molecule) upon Th0 membrane.
  • This re-directs transformation of Th0 into Th2 cells stimulating humoral response with antibody production.
  • The third signal for differentiation of Th0 into Th1 or Th2 cells ensues from alternative cytokine activation of T helper cells.
  • Type of cytokine secretion substantially depends on primary Ag recognition by APC via specialized pattern-recognizing receptors.
  • As mentioned above, stimulation of APC by TLR-4 activates the production of pro-inflammatory cytokines (IL-1, IL-12, IL-18, α-TNF, etc.) thereby causing Th1 differentiation. In contrast, Ag binding to TLR-2 in most cases triggers the release of IL-4, IL-10, IL-13 that promotes Th0 maturation into Th2 cell type.
  • Th1 and Th2 are characterized by the opposite type of cytokine secretion. In particular, major cytokines, produced by Th1 cells are γ-interferon, IL-2 and β-TNF, whereas cytokine array of Th2 encompasses IL-4, IL-5, IL-10, IL-13, and some others.
  • Th1/Th2 activity re-routes next immune reactions into a cell-mediated inflammatory response or towards B cell stimulation and antibody synthesis (humoral response).
  • Besides Th1/Th2 differentiation, some other types of specialized T helper cells become activated.
  • For instance, Th17 helper cells originate from Th0 under the activation by IL-23 from dendritic cells and by IL-21.
  • Follicular T helper cells TFH give rise from Th0 by the contact with follicular antigen-presenting B cells supported by stimulation with IL-21.

Activation and Differentiation of T Helper cells

Differentiation of T Helper cells