Early expansion of CD38+ICOS+ GC Tfh in draining lymph nodes during influenza vaccination immune response

Hannah Law; Melanie Mach; Annett Howe; Solange Obeid; Brad Milner; Cate Carey; Maxine Elfis; Bertha Fsadni; Katherine Ognenovska; Tri Giang Phan; Diane Carey; Yin Xu; Vanessa Venturi; John Zaunders; Anthony D Kelleher; C Mee Ling Munier

doi:10.1016/j.isci.2021.103656

Early expansion of CD38+ICOS+ GC Tfh in draining lymph nodes during influenza vaccination immune response

iScience. 2021 Dec 18;25(1):103656. doi: 10.1016/j.isci.2021.103656. eCollection 2022 Jan 21.

Authors

Hannah Law¹, Melanie Mach^{1

2}, Annett Howe¹, Solange Obeid³, Brad Milner³, Cate Carey¹, Maxine Elfis³, Bertha Fsadni⁴, Katherine Ognenovska¹, Tri Giang Phan^{5

6}, Diane Carey¹, Yin Xu¹, Vanessa Venturi¹, John Zaunders^{1

4}, Anthony D Kelleher^{1

3

4}, C Mee Ling Munier¹

Affiliations

¹ The Kirby Institute, UNSW Sydney, Sydney 2052, NSW, Australia.
² The University of Sydney, Sydney 2006, NSW, Australia.
³ St Vincent's Hospital Sydney, Sydney 2010, NSW, Australia.
⁴ St Vincent's Centre for Applied Medical Research (AMR), Sydney 2010, NSW, Australia.
⁵ Garvan Institute of Medical Research, Sydney 2010, NSW, Australia.
⁶ St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney 2010, NSW, Australia.

Abstract

T follicular helper (Tfh) cells provide critical help to B cells during the germinal center (GC) reaction to facilitate generation of protective humoral immunity. Accessing the human lymph node (LN) to study the commitment of CD4 T cells to GC Tfh cell differentiation during in vivo vaccine responses is difficult. We used ultrasound guided fine needle biopsy to monitor recall responses in axillary LNs to seasonal influenza vaccination in healthy volunteers. Specific expansion of GC cell subsets occurred exclusively within draining LNs five days postvaccination. Draining LN GC Tfh and precursor-Tfh cells express higher levels of CD38, ICOS, and Ki67, indicating they were significantly more activated, motile, and proliferating, compared to contralateral LN cells. These observations provide insight into the early expansion phase of the human Tfh lineage within LNs during a vaccine induced memory response and highlights early LN immune responses may not be reflected in the periphery.

Keywords: Cell biology; Components of the immune system; Immune response.