Generation of IL-3 secreting T helper cells is associated with microbial challenge at barriers and IL-1 family of cytokines

Abstract

Abstract Naive CD4+ T cells differentiate into distinct T helper subsets upon T cell receptor stimulation in a unique cytokine environment. The cytokine environment leads to the expression of subset-specific master transcription factor which enables secretion of cytokines characteristic of that subset and suppression of cytokines associated with other T helper subsets. We recently described that cutaneous Mycobacterium bovis BCG vaccination in mice induces a subset of T helper cells characterized by the secretion of IL-3. Here, we report that the induction of this subset of T helper cells is route dependent; cutaneous but not intravenous immunization with M. bovis BCG induced these cells. Similar results were obtained with a model of cutaneous Herpes Simplex Virus II infection. Infection with Herpes Simplex Virus by vaginal route or with M. tuberculosis by aerosol route induced these cells suggesting mucosal sites are conducive to their generation. In these scenarios, IL-3 secreting cells co-expressed GM-CSF, IFNγ, TNF and IL-2. In vitro polarization experiments showed that IL-3 secretion by CD4+ T cells was facilitated by IL-1 family of cytokines and suppressed by cytokines that induce Th1 and Th2 helper cells. The characteristic cytokine expression pattern and the dependence on route and cytokine environment of these cells support the idea that IL-3 secreting CD4+ T cells may represent a unique T helper subset.