Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

Abstract

Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.

• Authors: John F Ryan, Rachel Hovde, Jacob Glanville, Shu-Chen Lyu, Xuhuai Ji, Sheena Gupta, Robert J Tibshirani, David C Jay, Scott D Boyd, R Sharon Chinthrajah, Mark M Davis, Stephen J Galli, Holden T Maecker, Kari C Nadeau
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 9 Pg. E1286-95 (Mar 01 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 26811452 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens

Topics

• Allergens (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Humans
• Immunotherapy
• T-Lymphocyte Subsets