TY - JOUR
T1 - Multifunctional cytokine production marks influenza A virus-specific CD4 T cells with high expression of survival molecules
AU - Westerhof, Lotus M.
AU - Noonan, Jonathan
AU - Hargrave, Kerrie E.
AU - Chimbayo, Elizabeth T.
AU - Cheng, Zhiling
AU - Purnell, Thomas
AU - Jackson, Mark R.
AU - Borcherding, Nicholas
AU - MacLeod, Megan K.L.
N1 - Publisher Copyright:
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2023/11
Y1 - 2023/11
N2 - Cytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen-specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non-lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro-survival molecules, CD127 and Bcl2, than non-cytokine+ cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re-infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti-viral cytokine, interferon-γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
AB - Cytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen-specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non-lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro-survival molecules, CD127 and Bcl2, than non-cytokine+ cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re-infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti-viral cytokine, interferon-γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
KW - CD4 T cells
KW - Cytokine
KW - Immune memory
KW - Influenza virus
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85166437014&partnerID=8YFLogxK
U2 - 10.1002/eji.202350559
DO - 10.1002/eji.202350559
M3 - Article
C2 - 37490492
AN - SCOPUS:85166437014
SN - 0014-2980
VL - 53
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
M1 - 2350559
ER -