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About the Authors:
Courtney W. Mangus
Affiliations Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, Howard Hughes Medical Institute, National Institute of Health Research Scholars Program, Chevy Chase, Maryland, United States of America
Paul R. Massey
Affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Daniel H. Fowler
Affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Shoba Amarnath
* E-mail: [email protected]
Affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Introduction
CD4+ T helper subsets can differentiate into various lineages in response to environmental cues such as cytokines or ligand interactions. Of the various lineages of T helper subsets, Th9 cells are a recent addition. Th9 cells develop from CD4 precursors in response to TGF-β and IL-4 and are primarily characterized by their increased secretion of IL-9 [1]. While IL-9 producing CD4+ T cells were previously classified as Th2 cells [2], recent studies have shown that Th9 cells are a distinct lineage of T helper cells [1], [3]. Th9 cells have been implicated in various disease processes that have been associated with Th2 cells, including: helminth infection [4] [1], allergy [5] and asthma [6] [7]. However, Th9 cells can share mechanistic features of Th1 cells, as they have been associated with solid organ graft rejection [8], experimental peripheral neuritis [3] and anti-tumor responses [9]. On the other hand, the tolerogenic properties of Th9 cells were noted in a transplantation setting where IL-9 promoted allograft tolerance [10]. As such, there are somewhat conflicting data with respect to the role of Th9 cells in immunity, and no data exists concerning their potential role after experimental allogeneic bone marrow transplantation.
Rapamycin is an immunosuppressive drug that blocks cell surface signaling through inhibition of the kinase, mammalian target of rapamycin (mTOR) [11]. Although rapamycin can preferentially expand regulatory T cells (Tregs) [12] [13] in some models, we have shown that polarization towards Type I and Type II CD4+ T cells [14] [15], [16], [17] can be achieved in the presence of rapamycin provided that APC free co-stimulation is...