Th 1/Th 2 responses to drugs

Abstract

T lymphocytes can be characterized by their pattern of cytokine secretion and be divided into type I (Th l/Tc l) and type 2 (Th 2/Tc 2) subsets. The involvement of type-1 or type 2-like responses in sensitization has been studied in the mouse, with reference contact and respiratory contact sensitizers. One interesting feature with certain drugs, such as β-lactam antibiotics, is the diversity of clinical manifestations associated with immune-mediated hypersensitivity reactions in humans: immediate reactions such as urticaria, Quincke oedema and anaphylactic shock, and delayed hypersensitivity reactions, such as maculopapular rashes, allergic contact dermatitis and skin reactions of other types. In the mouse, Th 1 and Th 2 cytokines have been shown to regulate primary and secondary benzylpenicilloyl- (BPO-) specific antibody responses. Peripheral blood lymphocytes isolated from patients with a clear history of β-lactam allergy were assessed for type-1 and type-2 phenotypes. Immediate reactions involved mixed Th 1, Tc 1, and Tc 2 responses, whereas allergic contact dermatitis involved Tc 1 and Th 1 cells. Other delayed hypersensitivity reactions to β-lactams were restricted to Th 1 responses. It has been demonstrated that both CD4 + and CD8 +-lidocaine-specific T cell clones isolated from patients with allergic contact dermatitis produced IFN-γ, even though CD8 + clones only produce IFN-γ, while IFN-γ producing CD4 + cells concomitantly produced IL-5 and IL-4. Together these data illustrate the heterogeneity of drug-specific T-cell responses.