TY - JOUR
T1 - CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection
AU - Laidlaw, Brian J.
AU - Zhang, Nianzhi
AU - Marshall, Heather D.
AU - Staron, Mathew M.
AU - Guan, Tianxia
AU - Hu, Yinghong
AU - Cauley, Linda S.
AU - Craft, Joe
AU - Kaech, Susan M.
N1 - Funding Information:
We would like to acknowledge all members of the Kaech and Craft laboratories for helpful discussions and critical reading of the manuscript. This work was supported by grants from the NIH (RO1AI066232 [S.M.K.], R01AI074699 [S.M.K.], R01AR40072 [J.C.], P30AR053495 [J.C.], R21AR063942 [J.C.], T32AI07019 [B.J.L.]), F31AG07777 [B.J.L.], and the Howard Hughes Medical Institute [S.M.K., B.J.L.]).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/10/16
Y1 - 2014/10/16
N2 - Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4+ Tcells are important for the formation of functional lung-resident CD8+ Tcells after influenza virus infection. In the absence of CD4+ Tcells, CD8+ Tcells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8+ Tcells to the lung airways upon heterosubtypic challenge. CD4+ Tcell-derived interferon-γ was necessary for generating lung-resident CD103+ CD8+ Trm cells. Furthermore, expression of the transcription factor T-bet was increased in "unhelped" lung Trm cells, and areduction in T-bet rescued CD103 expression in the absence of CD4+ Tcell help. Thus, CD4+ Tcell-dependent signals are important to limit expression of T-bet and allow for the development of CD103+ CD8+ Trm cells in the lung airways following respiratory infection.
AB - Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4+ Tcells are important for the formation of functional lung-resident CD8+ Tcells after influenza virus infection. In the absence of CD4+ Tcells, CD8+ Tcells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8+ Tcells to the lung airways upon heterosubtypic challenge. CD4+ Tcell-derived interferon-γ was necessary for generating lung-resident CD103+ CD8+ Trm cells. Furthermore, expression of the transcription factor T-bet was increased in "unhelped" lung Trm cells, and areduction in T-bet rescued CD103 expression in the absence of CD4+ Tcell help. Thus, CD4+ Tcell-dependent signals are important to limit expression of T-bet and allow for the development of CD103+ CD8+ Trm cells in the lung airways following respiratory infection.
UR - http://www.scopus.com/inward/record.url?scp=84908127758&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.09.007
DO - 10.1016/j.immuni.2014.09.007
M3 - Article
C2 - 25308332
AN - SCOPUS:84908127758
VL - 41
SP - 633
EP - 645
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -