Th2 cell clonal expansion at diagnosis in human type 1 diabetes

Aditi Narsale; Francisco Almanza; Theo Tran; Breanna Lam; David Seo; Alisa Vu; S Alice Long; Laura Cooney; Elisavet Serti; Joanna D Davies

doi:10.1016/j.clim.2023.109829

Th2 cell clonal expansion at diagnosis in human type 1 diabetes

Clin Immunol. 2023 Dec:257:109829. doi: 10.1016/j.clim.2023.109829. Epub 2023 Oct 29.

Authors

Aditi Narsale¹, Francisco Almanza², Theo Tran³, Breanna Lam⁴, David Seo³, Alisa Vu⁵, S Alice Long⁶, Laura Cooney⁷, Elisavet Serti⁸, Joanna D Davies⁹

Affiliations

¹ San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA. Electronic address: anarsale@sdbri.org.
² San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA. Electronic address: falmanza@sdbri.org.
³ San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA.
⁴ San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA. Electronic address: bhlam@mit.edu.
⁵ San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA. Electronic address: avu@sdbri.org.
⁶ Benaroya Research Institute, 1201 9(th) Ave, Seattle, WA 98101, USA. Electronic address: along@benaroyaresearch.org.
⁷ Immune Tolerance Network, Ann Arbor, MI, USA. Electronic address: lcooney@immunetolerance.org.
⁸ Immune Tolerance Network, Bethesda, MD, USA. Electronic address: ESertiChrisos@hivresearch.org.
⁹ San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA. Electronic address: jdavies@sdbri.org.

PMID: 37907122
DOI: 10.1016/j.clim.2023.109829

Abstract

Soon after diagnosis with type 1 diabetes (T1D), many patients experience a period of partial remission. A longer partial remission is associated with a better response to treatment, but the mechanism is not known. The frequency of CD4⁺CD25⁺CD127^hi (127-hi) cells, a cell subset with an anti-inflammatory Th2 bias, correlates positively with length of partial remission. The purpose of this study was to further characterize the nature of the Th2 bias in 127-hi cells. Single cell RNA sequencing paired with TCR sequencing of sorted 127-hi memory cells identifies clonally expanded Th2 clusters in 127-hi cells from T1D, but not from healthy donors. The Th2 clusters express GATA3, GATA3-AS1, PTGDR2, IL17RB, IL4R and IL9R. The existence of 127-hi Th2 cell clonal expansion in T1D suggests that disease factors may induce clonal expansion of 127-hi Th2 cells that prolong partial remission and delay disease progression.

Keywords: Autoimmunity; T cells; Th1/Th2; Transcriptome.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Diabetes Mellitus, Type 1* / genetics
Humans
Th2 Cells*

Grants and funding

UM1 AI109565/AI/NIAID NIH HHS/United States