Role of Effector Cells (CCR7⁻CD27⁻) and Effector-Memory Cells (CCR7⁻CD27⁺) in Drug-Induced Maculopapular Exanthema

Abstract

Maculopapular exanthema (MPE) induced by drugs is a T-cell mediated reaction and effector cells may play an important role in its development. We assessed the effector and cutaneous homing phenotype in peripheral blood cells from allergic patients after drug stimulation. This study included 10 patients and 10 controls. The effector phenotype (CCR7−CD27+/−), chemokine receptors (CCR4 and CCR10), and activation (CD25low) and regulatory markers (CD25high) were measured by flow cytometry in both peripheral blood mononuclear cells (PBMCs) and CD4-T-lymphocytes. Proliferation was determined by 5-(−6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) assay and the migratory capacity by a chemotaxis assay using CCL17 and CCL27. Compared to controls, CCR7−CD27− cells were increased in patients without (p=0.003) and with drug stimulation (p<0.001) and had significantly higher proliferation (p=0.010). CCR10 expression was increased in patients after drug stimulation in total and memory CD27+ T-cells. Lymphocyte migration with CCL27 was higher in patients with drug stimulation (p=0.048), with a decrease in CCR7−CD27− (p<0.0001) and an increase in CCR7−CD27+ (p=0.017). In patients, CD4-T-lymphocytes were significantly activated after drug stimulation (p<0.001). In conclusion, we show that effector memory CD4+ T-cells (CCR7−CD27+) respond specifically to the drug responsible for MPE and confirm previous data about the involvement of CCR10 in cell trafficking to the skin.

Cholesterol, Cytokines and Diseases

“…In addition, IL-18, particularly in combination with IL-12, is a proximal inducer and regulator of the expression of IFN-y, a major proinflammatory cytokine, during atherogenesis. Interestingly, IL-18 induces IFN-y expression not only in T cells (49)(50)(51)(52)(53), but also in macrophages and, surprisingly, even in SMCs, thus activating in a paracrine mode several proinflammatory pathways operating during atherogenesis (54)(55)(56)(57).…”

Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment

“…In AGEP, another severe delayed drug-induced reaction, lymphocytes have a dual role as cytotoxic agents and inducing migration of neutrophils to the skin by producing IL-8 (Britschgi & Pichler, 2002;Hertl et al, 1993;Padial et al, 2004;Yawalkar et al, 2000). At the acute phase of TEN, T cells are recruited to the skin, producing cytotoxic markers such as perforin and granzyme B (Fernandez et al, 2010;Mayorga et al, 2003;Pichler, 2003;Posadas et al, 2002;Torres et al, 2006;Zawodniak et al, 2010), and they express high levels of CCR10 and their chemokine CCL27 (Tapia et al, 2004). As mentioned, this monitoring is useful in order to understand not only the underlying mechanisms but also to assess the response to treatment.…”

Drug Hypersensitivity

“…In AGEP, another severe delayed drug-induced reaction, lymphocytes have a dual role as cytotoxic agents and inducing migration of neutrophils to the skin by producing IL-8 (Britschgi & Pichler, 2002;Hertl et al, 1993;Padial et al, 2004;Yawalkar et al, 2000). At the acute phase of TEN, T cells are recruited to the skin, producing cytotoxic markers such as perforin and granzyme B (Fernandez et al, 2010;Mayorga et al, 2003;Pichler, 2003;Posadas et al, 2002;Torres et al, 2006;Zawodniak et al, 2010), and they express high levels of CCR10 and their chemokine CCL27 . As mentioned, this monitoring is useful in order to understand not only the underlying mechanisms but also to assess the response to treatment.…”