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Available online /content/11/6/257 Review Heterogeneity of human effector CD4+ T cells Francesco Annunziato and Sergio Romagnani Center of Excellence for Research, Transfer of Research and High Education for the Development of Novel Therapies (DENOthe), Department of Internal Medicine, University of Florence, Viale Morgagni 85, Florence 50134, Italy Corresponding author: Sergio Romagnani, s.romagnani@dmi.unifi.it Published: 9 December 2009 Arthritis Research Therapy 2009, 11:257 (doi:10.1186/ar2843) This article is online at /content/11/6/257 © 2009 BioMed Central Ltd Abstract induce inflammatory reactions mainly characterized by the For many years the heterogeneity of CD4+ T-helper (Th) cells has activation of macrophages. The prototypic cell-mediated been limited to Th1 and Th2 cells, which have been considered not immune response was considered to be the skin papular only to be responsible for different types of protective responses, reaction induced by intradermal injection of tuberculin or but also for the pathogenesis of many disorders. Th1 cells are purified protein derivative (PPD) in animals infected with indeed protective against intracellular microbes and they are tubercular bacilli or in humans naturally infected by Myco- thought to play a pathogenic role in organ-specific autoimmune bacterium tuberculosis or vaccinated with Bacillus Calmette- and other chronic inflammatory disorders. Th2 cells provide