• Naeun Lee, Sungyong You, Min Sun Shin, Won-Woo Lee, Ki Soo Kang, Sang Hyun Kim, Wan-Uk Kim, Robert J Homer, Min-Jong Kang, Ruth R Montgomery, Charles S Dela Cruz, Albert C Shaw, Patty J Lee, Geoffrey L Chupp, Daehee Hwang, and Insoo Kang.
• 1 Department of Internal Medicine and.
• Am. J. Respir. Crit. Care Med.. 2014 Dec 15;190(12):1383-94.

RationaleCytokine 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.ObjectivesTo determine whether and how IL-6Rα defines a distinct effector memory (EM) CD8+ T-cell population in health and disease.MethodsEM 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 ResultsA 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.ConclusionsHuman 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.

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