Molecular mechanisms of CD8+ T cell-mediated delayed hypersensitivity: Implications for allergies, asthma, and autoimmunity

Delayed-type hypersensitivity (DTH) is defined as the recruitment of T cell s into tissues to be activated by antigen-presenting cells to produce cytok ines that mediate Local inflammation. CD8+ T cells are now known to mediate DTH responses in allergic contact dermatitis, drug eruptions, asthma, and autoimmune diseases. This inflammatory effector capability of CD8+ cytotoxi c T cells was previously poorly recognized, but there is now considerable e vidence that these diseases may be mediated by CD8+ DTH. The difference bet ween CD8+ T cells and CD4+ T cells mediating DTH relates to the molecular m echanisms by which antigens are processed and presented to the T cells. Ant igens external to the cell are phagocytosed and processed for presentation on MHC class II molecules (eg, HLA-DR) to CD4+ T cells. In contrast, intern al cytoplasmic antigens are processed by the endogenous pathway for present ation on MHC class I molecules (eg, HLA-A, -B, and -C) to CD8+ T cells, Ext ernal allergens can also enter the endogenous pathway to be presented to CD 8+ T cells. These include many contact sensitizers, chemical and protein re spiratory allergens, viral antigens, metabolic products of drugs, and autoa ntigens. The resulting CD8+ T-cell response explains the role of CD8+ T-cel l DTH mechanisms in allergic contact dermatitis, asthma, drug eruptions, an d autoimmune diseases.