ThG Cells: A Distinct T Helper Cell Subset with Lineage Characteristics

Javad Rasouli, Thomas Jefferson University

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by the accumulation of immune cells in the central nervous system (CNS). GM-CSF is a proinflammatory cytokine that is mainly expressed by CD4+ T cells. GM-CSF is necessary for the development of CNS autoimmunity in an animal model of MS, EAE, suggesting that GM-CSF also plays an essential role in the pathogenesis of MS. We showed that MS patients have higher frequencies of GM-CSF+ Th cells. These numbers were normalized by IFN- therapy. IFN- suppressed GM-CSF expression by Th cells and, consequently, EAE progression via induction of IL-10 and suppression of IL-1. IFN- derives its suppressive effect through myeloid cells, and it suppresses disease only when monocytes express IFNAR1. We also found a unique subset of GM-CSF+ Th cells in the peripheral blood (PB) of healthy donors and MS patients. We designated these cells that expressed GM-CSF but lacked lineage-specific cytokines and transcription factors as “ThG” cells. ThG frequencies are increased in PB of MS patients in the periphery and in the CNS of EAE mice. ThG cells that had a unique transcriptome were stable in culture. ThG cells acquire Th1 phenotype after stimulation with Th1-inducing cytokines. T-bet mediated this phenotype switch; however, T-bet was not necessary for the development of ThG cells. ThG cells were pathogenic, and they required T-bet for their encephalitogenicity. Finally, ThG, similar to other Th cells, ceased expression of GM-CSF without other major changes in their phenotype. Taken as a whole, our data provide evidence that targeting GM-CSF+ Th cells can be one of the therapeutic mechanisms for the treatment of MS. ThG cells, as a new lineage of Th cells, contribute to the pathophysiology of CNS inflammation, and could be a novel target for therapy in MS and autoimmunity in general.

Subject Area

Immunology

Recommended Citation

Rasouli, Javad, "ThG Cells: A Distinct T Helper Cell Subset with Lineage Characteristics" (2020). ETD Collection for Thomas Jefferson University. AAI27740402.
https://jdc.jefferson.edu/dissertations/AAI27740402

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