IL-6 receptor α defines effector memory CD8+ T cells producing Th2 cytokines and expanding in asthma.
BACKGROUND
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.


OBJECTIVE
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.


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.
1 Department of Internal Medicine and.
Naeun
N
Lee
Sungyong
S
You
Min Sun
MS
Shin
Won-Woo
WW
Lee
Ki Soo
KS
Kang
Sang Hyun
SH
Kim
Wan-Uk
WU
Kim
Robert J
RJ
Homer
Min-Jong
MJ
Kang
Ruth R
RR
Montgomery
Charles S
CS
Dela Cruz
Albert C
AC
Shaw
Patty J
PJ
Lee
Geoffrey L
GL
Chupp
Daehee
D
Hwang
Insoo
I
Kang
D001249:Asthma / Q000503:physiopathology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology*; D015848:Interleukin-5 / Q000502:physiology*; D053698:Interleukin-6 Receptor alpha Subunit / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018793:Interleukin-13; D015848:Interleukin-5; D053698:Interleukin-6 Receptor alpha Subunit
CD8+ T cells; IL-6 receptor; Th2 cytokines; asthma; human