Figure 3.

Immunoregulatory molecules and cytokines implicated in contact hypersensitivity (CHS). During sensitization, the skin-penetrating hapten is processed by Langerhans cells (LCs) or dermal dendritic cells. GITR-GTRL interactions between keratinocytes and LCs enhance keratinocyte secretion of cytokines, which aid maturation and migration of LCs to the skin-draining lymph node. In the SDLN, in addition to hapten presentation, several costimulatory and coinhibitory interactions, e.g., CD40-CD40L, OX40L-OX40, B7-CD28, and B7-CTLA-4, between the APC and the naïve T cell take place. The hapten-specific effector T cells, predominantly CD8+ cytotoxic T cells, infiltrate the skin and elicit the CHS response upon hapten re-exposure. The presence of Tregs and several coinhibitory receptors on CD8+ T cells and CD8+ Trm cells are associated with decreased CHS response. APC, antigen presenting cell; BTLA, B- and T-lymphocyte attenuator; CD40L, CD40 ligand; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; Gal-9, galectin-9; GITR(L), glucocorticoid induced TNF receptor (ligand); HEVM, herpes virus entry mediator; IL-1β, interleukin-1 beta; LC, Langerhans cell; MHC, major histocompatibility complex; OX40L, OX40 ligand; PD-1, programmed cell death protein 1; PD-L1, programmed death ligand-1; SDLN, skin-draining lymph nodes; TCR, T cell receptor; TIM-3, T-cell immunoglobulin mucin-3; TNF, tumor necrosis factor; Treg, regulatory T cell; Trm, tissue-resident memory T cell.