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Type 1- and Type 2-Like Lesional Skin-Derived Mycobacterium leprae-Responsive T Cell Clones Are Characterized by Coexpression of IFN-/TNF- and IL-4/IL-5/IL-13, Respectively¹

Claudia E. Verhagen^*,, Tineke C. T. M. van der Pouw Kraan, Anita A. M. Buffing^*,, Mohamed A. Chand, William R. Faber^*, Lucien A. Aarden and Pranab K. Das^2,*,

Departments of ^* Dermatology and Pathology, Academic Medical Center, and Department of AutoImmune Diseases, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, Amsterdam, The Netherlands

In an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN- and IL-4 expression. To explore whether other cytokines are coproduced along with IFN- and IL-4, we investigated the secretion of a panel of other cytokines (TNF-, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-/TNF- (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-/TNF-, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.

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