RATIONALE: Cytokine receptors can be markers defining different T-cell subsets and considered as therapeutic targets. The association of IL-6 and IL-6 receptor α (IL-6Rα) with asthma was reported, suggesting their involvement in asthma. OBJECTIVES: To determine whether and how IL-6Rα defines a distinct effector memory (EM) CD8+ T-cell population in health and disease. METHODS: EM CD8+ T cells expressing IL-6Rα (IL-6Rα(high)) were identified in human peripheral blood and analyzed for function, gene, and transcription factor expression. The relationship of these cells with asthma was determined using blood and sputum. MEASUREMENTS AND MAIN RESULTS: A unique population of IL-6Rα(high) EM CD8+ T cells was found in peripheral blood. These cells that potently proliferated, survived, and produced high levels of the Th2-type cytokines IL-5 and IL-13 had increased levels of GATA3 and decreased levels of T-bet and Blimp-1 in comparison with other EM CD8+ T cells. In fact, GATA3 was required for IL-6Rα expression. Patients with asthma had an increased frequency of IL-6Rα(high) EM CD8+ T cells in peripheral blood compared with healthy control subjects. Also, IL-6Rα(high) EM CD8+ T cells exclusively produced IL-5 and IL-13 in response to asthma-associated respiratory syncytial virus and bacterial superantigens. CONCLUSIONS: Human IL-6Rα(high) EM CD8+ T cells is a unique cell subset that may serve as a reservoir for effector CD8+ T cells, particularly the ones producing Th2-type cytokines, and expand in asthma.
RATIONALE: Cytokine receptors can be markers defining different T-cell subsets and considered as therapeutic targets. The association of IL-6 and IL-6 receptor α (IL-6Rα) with asthma was reported, suggesting their involvement in asthma. OBJECTIVES: To determine whether and how IL-6Rα defines a distinct effector memory (EM) CD8+ T-cell population in health and disease. METHODS: EM CD8+ T cells expressing IL-6Rα (IL-6Rα(high)) were identified in human peripheral blood and analyzed for function, gene, and transcription factor expression. The relationship of these cells with asthma was determined using blood and sputum. MEASUREMENTS AND MAIN RESULTS: A unique population of IL-6Rα(high) EM CD8+ T cells was found in peripheral blood. These cells that potently proliferated, survived, and produced high levels of the Th2-type cytokines IL-5 and IL-13 had increased levels of GATA3 and decreased levels of T-bet and Blimp-1 in comparison with other EM CD8+ T cells. In fact, GATA3 was required for IL-6Rα expression. Patients with asthma had an increased frequency of IL-6Rα(high) EM CD8+ T cells in peripheral blood compared with healthy control subjects. Also, IL-6Rα(high) EM CD8+ T cells exclusively produced IL-5 and IL-13 in response to asthma-associated respiratory syncytial virus and bacterial superantigens. CONCLUSIONS:Human IL-6Rα(high) EM CD8+ T cells is a unique cell subset that may serve as a reservoir for effector CD8+ T cells, particularly the ones producing Th2-type cytokines, and expand in asthma.
Entities:
Keywords:
CD8+ T cells; IL-6 receptor; Th2 cytokines; asthma; human
Authors: S Ying; M Humbert; J Barkans; C J Corrigan; R Pfister; G Menz; M Larché; D S Robinson; S R Durham; A B Kay Journal: J Immunol Date: 1997-04-01 Impact factor: 5.422
Authors: Aysefa Doganci; Tatjana Eigenbrod; Norbert Krug; George T De Sanctis; Michael Hausding; Veit J Erpenbeck; El-Bdaoui Haddad; Hans A Lehr; Edgar Schmitt; Tobias Bopp; Karl-J Kallen; Udo Herz; Steffen Schmitt; Cornelia Luft; Olaf Hecht; Jens M Hohlfeld; Hiroaki Ito; Norihiro Nishimoto; Kazuyuki Yoshizaki; Tadamitsu Kishimoto; Stefan Rose-John; Harald Renz; Markus F Neurath; Peter R Galle; Susetta Finotto Journal: J Clin Invest Date: 2005-02 Impact factor: 14.808
Authors: Sang-Heon Cho; Luminita A Stanciu; Stephen T Holgate; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2004-10-22 Impact factor: 21.405
Authors: Yunqi Wang; Ichiro Misumi; Ai-Di Gu; T Anthony Curtis; Lishan Su; Jason K Whitmire; Yisong Y Wan Journal: Nat Immunol Date: 2013-05-26 Impact factor: 25.606
Authors: Min Sun Shin; Sungyong You; Youna Kang; Naeun Lee; Seung-Ah Yoo; Kieyoung Park; Ki Soo Kang; Sang Hyun Kim; Subhasis Mohanty; Albert C Shaw; Ruth R Montgomery; Daehee Hwang; Insoo Kang Journal: J Immunol Date: 2015-08-14 Impact factor: 5.422
Authors: Jutamas Suwanpradid; Michael Shih; Lauren Pontius; Bin Yang; Anastasiya Birukova; Emma Guttman-Yassky; David L Corcoran; Loretta G Que; Robert M Tighe; Amanda S MacLeod Journal: J Immunol Date: 2017-07-26 Impact factor: 5.422
Authors: Junghee J Shin; Jason Catanzaro; Jennifer R Yonkof; Ottavia Delmonte; Keith Sacco; Min Sun Shin; Srikar Reddy; Paula J Whittington; Gary Soffer; Peter J Mustillo; Kathleen E Sullivan; Luigi D Notarangelo; Roshini S Abraham; Neil Romberg; Insoo Kang Journal: J Clin Immunol Date: 2021-01-26 Impact factor: 8.317
Authors: Alisha M Smith; Nathan Harper; Justin A Meunier; Anne P Branum; Fabio Jimenez; Lavanya Pandranki; Andrew Carrillo; Charles S Dela Cruz; Marcos I Restrepo; Diego J Maselli; Cynthia G Rather; Anna H Heisser; Daniel A Ramirez; Weijing He; Robert A Clark; Charles P Andrews; Scott E Evans; Jacqueline A Pugh; Nu Zhang; Grace C Lee; Alvaro G Moreira; Leopoldo N Segal; Robert M Ramirez; Robert L Jacobs; Muthu Saravanan Manoharan; Jason F Okulicz; Sunil K Ahuja Journal: J Allergy Clin Immunol Date: 2021-01-23 Impact factor: 14.290
Authors: Alisha M Smith; Robert M Ramirez; Nathan Harper; Fabio Jimenez; Anne P Branum; Justin A Meunier; Lavanya Pandranki; Andrew Carrillo; Caitlyn Winter; Lauryn Winter; Cynthia G Rather; Daniel A Ramirez; Charles P Andrews; Marcos I Restrepo; Diego J Maselli; Jacqueline A Pugh; Robert A Clark; Grace C Lee; Alvaro G Moreira; Muthu Saravanan Manoharan; Jason F Okulicz; Robert L Jacobs; Sunil K Ahuja Journal: Allergy Date: 2021-10-22 Impact factor: 14.710