T Cell Assessment in Allergic Drug Reactions during the Acute Phase According to the Time of Occurrence

Abstract

Allergic drug reactions can be classified as immediate, accelerated or delayed. This classification usually correlates with the mechanism involved: immediate reactions are IgE mediated and delayed reactions are T cell dependent. We analyzed lymphocyte involvement in patients with these reactions by determining cell subpopulations, activation state and skin homing receptor expression (CLA) in blood and skin. Patients with immediate, accelerated and delayed reactions were evaluated during the acute phase and after resolution. Controls taking drugs were included. Phenotypic immunofluorescence analysis was done by flow cytometry in peripheral blood, and by immunohistochemistry in skin for delayed reactions. Forty-six patients were included, 17 with immediate reactions, 10 accelerated and 19 delayed. At the acute phase CLA was significantly increased in delayed reactions and HLA-DR in all three types of reaction. In the severest delayed reactions, Steven-Johnson/Lyell syndromes, the CD4 subsets were increased in peripheral blood and skin compared to maculopapular exanthemas and urticaria and HLA-DR when compared with urticaria. In maculopapular exanthemas CLA was significantly increased in peripheral blood and skin compared to urticaria and the severe reactions. We found that T-cells are implicated, besides delayed reactions, in immediate and accelerated reactions. In delayed reactions there is a parallelism between results found in skin and peripheral blood with a higher participation of CD4+ cells the more severe the reaction.

Potential involvement of dendritic cells in delayed-type hypersensitivity reactions to β-lactams

“…30 This in vitro response is similar to in vivo data during the reaction, showing that in DTH responses to amoxicillin a mononuclear perivascular infiltrate composed mainly of CD4 cells expresses activation markers and cutaneous homing receptor. 28,29,31 Regarding the functional significance of these lymphocytes, CD4 T cells regulate CD8 T cell-mediated cutaneous immune responses by restricting the development of effector CD8 T cells. 32 This could explain why we detected lower IFN-g concentrations when DCs acted as APCs compared with monocytes or B cells.…”

Monitoring the acute phase response in non-immediate allergic drug reactions

“…by analysing the two compartments it was found that in delayed reactions there is a parallel between results found in skin and peripheral blood, with a higher participation of CD4þ cells the more severe the reaction [64]. Other reports have shown that most CLA-positive T cells express skin-homing chemokine receptors such as CCR4 and CCR10 [50,65,66] and an increase in chemokine CCL27 production in keratinocytes, which correlates with the CCR10 expression in memory T lymphocytes and also with severity [21].…”

Cutaneous symptoms in drug allergy: what have we learnt?

“…In MPE, a mononuclear infiltrate can be found in the perivascular dermis, with T lymphocytes, mainly CD4 þ T cells [12,13,14 ], with the presence of neutrophils and occasionally eosinophils [15]. Recent skin patch test studies have shown CD8 þ T cells in the dermoepidermal junction [16][17][18] with a cytotoxic capacity [10,[19][20][21].…”