Chronic Lymphocytic Leukaemia-Associated Expansion of T Follicular Helper and T Follicular Regulatory Cells Is Normalised in Patients Receiving Chemotherapy

  • Šlisere, B. (Speaker)
  • Dzidra Bubire (Co-author)
  • Arturs Uzars (Co-author)
  • Alla Rivkina (Co-author)
  • Auziņa, D. (Co-author)
  • Dārta Balode (Co-author)
  • Ludmila Beļajeva (Co-author)
  • Larisa Zariņa (Co-author)
  • Oļeiņika, K. (Co-author)
  • Lejniece, S. (Co-author)

Activity: Talk or presentation types › Poster presentation

Description

Infections are a significant cause of morbidity and mortality in chronic lymphocytic leukaemia (CLL), however, specific mechanisms that underlie dysregulated immunity in CLL remain largely uncharacterized. The quality of B cell response to infection and vaccination is fine-tuned by specialized subsets of T cells that promote (T follicular helper, Tfh) or suppress (T follicular regulatory, Tfr) antibody production. We determined circulating Tfh and Tfr frequencies and absolute numbers in CLL patients that were untreated (Unt-CLL) or received chemotherapy (ChTx-CLL). We further interrogated immunoglobulin (Ig) levels as a surrogate marker for productive B cell responses.. In a cross-sectional study peripheral blood was collected from Unt-CLL (n=19) and ChTx-CLL (n=7) patients and age-matched healthy controls (HC, n=14). Flow cytometry was used to determine Tfh (CD3+CD4+CD45RA-CXCR5+) and Tfr (CD3+CD4+CD45RA-CXCR5+FOXP3+) frequencies. IgA, IgG, and IgM levels were assessed in serum by immunoturbidimetry. Flow cytometry data were analyzed using FlowJo v10.8 software and nonparametric statistical analysis conducted in GraphPad Prism 9.4.This work is funded by the Latvian Council of Science Fundamental and Applied Research Project Grant No Izp-2022/1-0080.. While the abundance of both Tfh and Tfr cells was comparable in ChTx-CLL patients and HCs, these T cell subsets were significantly elevated in Unt-CLL compared to HCs. Unexpectedly, in Unt-CLL we also found negative correlations between IgA and both Tfh and Tfr frequencies; this was unique to the IgA antibody class.. CLL patients present with an expansion of Tfh and Tfr cells that is apparently normalised by chemotherapy. The negative correlation between IgA antibody levels and Tfh cells in Unt-CLL patients suggests that, despite their expansion, Tfh cells are dysfunctional. Indeed, it has been postulated that in vivo Tfh-CLL B cell interactions support malignant B cell expansion and impede normal B cell responses; our future work will address the mechanisms by which this occurs.
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

Related content