T-cell STAT3 is required for the maintenance of humoral immunity to LCMV.
STAT3 is a critical transcription factor activated downstream of cytokine signaling and is integral for the function of multiple immune cell types. Human mutations in STAT3 cause primary immunodeficiency resulting in impaired control of a variety of infections, including reactivation of latent viruses. In this study, we investigate how T-cell functions of STAT3 contribute to responses to viral infection by inducing chronic lymphocytic choriomeningitis virus (LCMV) infection in mice lacking STAT3 specifically in T cells. Although mice with conditional disruption of STAT3 in T cells were able to mount early responses to viral infection similar to control animals, including expansion of effector T cells, we found generation of T-follicular helper (Tfh) cells to be impaired. As a result, STAT3 T cell deficient mice produced attenuated germinal center reactions, and did not accumulate bone marrow virus specific IgG-secreting cells, resulting in failure to maintain levels of virus-specific IgG or mount neutralizing responses to LCMV in the serum. These effects were associated with reduced control of viral replication and prolonged infection. Our results demonstrate the importance of STAT3 in T cells for the generation of functional long-term humoral immunity to viral infections.
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
David R
DR
McIlwain
Melanie
M
Grusdat
Vitaly I
VI
Pozdeev
Haifeng C
HC
Xu
Prashant
P
Shinde
Colin
C
Reardon
Zhenyue
Z
Hao
Marc
M
Beyer
Andreas
A
Bergthaler
Dieter
D
Häussinger
Garry P
GP
Nolan
Karl S
KS
Lang
Philipp A
PA
Lang
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002908:Chronic Disease; D015870:Gene Expression; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000096:biosynthesis*; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology* / Q000821:virology; D014779:Virus Replication
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
Chronic infection; Humoral immunity; LCMV; STAT3; T follicular helper cells