Basic and clinical immunology
Potential involvement of dendritic cells in delayed-type hypersensitivity reactions to β-lactams

https://doi.org/10.1016/j.jaci.2006.07.013Get rights and content

Background

Although the involvement of T cells in delayed reactions to drugs has been studied, little is known about the interaction between the drug and the antigen-presenting cells. Dendritic cells (DCs) are professional antigen-presenting cells essential for initiating T-cell responses. Their ability is regulated in a process known as maturation, by which they modulate the effector immune response.

Objectives

We studied the role of DCs in subjects who had a delayed-type hypersensitivity reaction to amoxicillin to assess the effect on the pattern of maturation and determine the capacity of DCs to activate T lymphocytes.

Methods

We examined the consequences of the interaction between monocyte-derived DCs, lymphocytes, and amoxicillin by means of phenotypic and functional studies, including endocytosis, proliferation, and cytokine production.

Results

Amoxicillin drove DCs from hypersensitive subjects to a phenotypic and functional semimature status, inducing a T-cell proliferation response.

Conclusions

In delayed reactions to amoxicillin, DCs play a relevant role in inducing the T-cell responses. These results are useful not only to understand the mechanism but potentially as a possible approach to diagnosis.

Clinical implications

A better understanding of T-cell and DC involvement in delayed-type hypersensitivity reactions is needed. This in vitro assay might provide clues to the diagnostic evaluation of patients allergic to penicillins.

Section snippets

Patients and control subjects

Nine patients (mean age, 49.44 ± 7.37 years) with DTH reactions to amoxicillin and a positive delayed intracutaneous test response to amoxicillin were studied.16, 17 All patients had maculopapular exanthema. Table I shows their clinical characteristics, the time interval between the reaction and sample collection (mean, 156.67 ± 74.91 months), and the results of the allergologic work-up.

Control subjects were composed of 8 healthy sex- and age-matched subjects with no history of hypersensitivity

Amoxicillin induced phenotypic and functional changes in imDCs from hypersensitive patients

LPS and TNF-α produced a significant upregulation in the MFI and the percentage of imDCs expressing HLA-DR, CD86, CD80, and CD83 in both patients and control subjects at 24, 48, and 72 hours (Fig 1), with no significant differences between the 2 groups, indicating that DCs were similar at baseline and responded at equal levels to the maturation stimuli generated by TNF-α or LPS. In hypersensitive patients the results obtained from imDCs stimulated for 72 hours with amoxicillin at 50 and 250

Discussion

The aim of this study was to determine whether amoxicillin induces any influence on imDCs in subjects who had a T cell–mediated DTH response. Results showed that amoxicillin increased the expression of DC maturation and activation markers (HLA-DR, CD86, and CD80). Furthermore, amoxicillin-treated imDCs acquired a higher T cell–stimulatory capacity, illustrated by increased proliferation of allogeneic T cells. Also, maturational changes (endocytosis capacity) were noted after amoxicillin-imDC

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    Supported by grants from Fondo de Investigación Sanitaria (PIO5290) and Junta de Andalucia (199/04).

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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