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Association of Asthma Severity and Bronchial Hyperresponsiveness With a Polymorphism

Association of Asthma Severity and Bronchial Hyperresponsiveness With a PolymorphismBronchial asthma is characterized by the infiltration of inflammatory cells into the airway submucosa. While the precise mechanisms by which inflammatory cells are recruited into the lungs are not fully understood, increasingly available evidence suggests that the activation of antigen-specific CD4+ T cells of the type 2 T-helper (Th2) subset in the lungs, which results in interleukin (IL)-5 secretion plays a major role in asthmatic airway inflam-mation comments canadianneighborpharmacy.com. CD4+ T-cell activation leading to cytokine production and effector function requires two signals from the antigen-presenting cell (APC). The first signal is triggered by the interaction between antigen-specific T-cell receptor and peptide-major histocompatibility complex II complexes on APCs. The second signal or “costimulatory” signal is triggered by CD80 (B7-1) and CD86 (B7-2) of the APC binding to the CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 of the T lymphocyte. In the absence of costimulatory signals, the T-cell-dependent immune response is greatly diminished, or even eliminat-ed and costimulatory signals may, therefore, fulfill a valuable role in T-lymphocyte activation, type 1 T-helper (Th1) or Th2 cell differentiation, and the production of various cytokines.
CTLA-4 is a second costimulatory molecule and is a homolog of CD28. It is expressed only on activated T cells, binds to accessory molecule B7, and mediates T-cell-dependent immune response. Signaling through CTLA-4 may down-regulate Th1 cell proliferation by inhibiting the production of IL-2 and IL-2 receptor expression. However, the role of CTLA-4 remains uncertain, with some studies suggesting that CTLA-4 might also deliver a positive signal to Th2 cell activation. Disruption of this delicate balance of immune regulation could lead to autoimmune diseases or atopic diseases. Therefore, CTLA-4 is considered to be important in the development of many of the immunologic and physiologic features of asthma.