IL-4 induces CD22 expression to restrain the effector program of virtual memory T cells
Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8<sup>+</sup> T cells (T<sub>VM</sub> cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent T<sub>VM</sub> cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8<sup>+</sup> T cells to identify pathways that control IL-4-dependent T<sub>VM</sub> cell responses. Gene signature analysis of CD8<sup>+</sup> T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced T<sub>VM</sub> cells. CD22<sup>+</sup> T<sub>VM</sub> cells were enriched for interferon-γ and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8<sup>+</sup> T cell effector program, resulting in reduced responsiveness of CD22<sup>+</sup> T<sub>VM</sub> cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of T<sub>VM</sub> cells that is counterinhibited by CD22.
Authors
- Fabienne Andris (ORCID: https://orcid.org/0000-0002-8644-1020)
- Gert Van Isterdael (ORCID: https://orcid.org/0000-0001-6626-1316)
- Benjamin G Dewals (ORCID: https://orcid.org/0000-0003-1497-0799)
- Ariel Madrigal
- Garrie Peng (ORCID: https://orcid.org/0009-0009-0484-8926)
- Alípio Barbosa Balthazar
- Qiang Baï (ORCID: https://orcid.org/0000-0001-7423-0712)
- Hamed Shateri Najafabadi (ORCID: https://orcid.org/0000-0003-2735-4231)
- David Vermijlen (ORCID: https://orcid.org/0000-0002-7605-8845)
- Sarah J. Meyer (ORCID: https://orcid.org/0000-0001-8286-132X)
- Julie Van Duyse (ORCID: https://orcid.org/0000-0001-7170-0061)
- Lucia Rodriguez-Rodriguez (ORCID: https://orcid.org/0000-0001-8251-8118)
- Arnaud Lavergne (ORCID: https://orcid.org/0000-0003-4817-3202)
- Meijiao Gong
- Guillem Sanchez Sanchez (ORCID: https://orcid.org/0000-0001-9919-1748)
- Georgios Petrellis (ORCID: https://orcid.org/0000-0002-6444-4378)
- Thomas Marichal (ORCID: https://orcid.org/0000-0003-1688-6291)
- Irah L. King (ORCID: https://orcid.org/0000-0001-6990-7231)
- Ophélie Piedfort (ORCID: https://orcid.org/0000-0002-1262-4123)
- Lars Nitschke
- Bénédicte Machiels (ORCID: https://orcid.org/0000-0003-1326-3865)
- Brunette Katsandegwaza (ORCID: https://orcid.org/0000-0002-9659-4485)
- Bin Yang (ORCID: https://orcid.org/0009-0002-5697-3226)
Institutions
- Université Libre de Bruxelles (BE)
- Inserm (FR)
- University of Liège (BE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Université de Montpellier (FR)
- McGill University Health Centre (CA)
- Ghent University (BE)
- Physiologie et Médecine Expérimentale du Coeur et des Muscles (FR)
- Institute of Pathology and Genetics (BE)
- McGill Genome Centre (CA)
- VIB-UGent Center for Inflammation Research (BE)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Institute of Infection and Immunity (CA)
- McGill University (CA)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1126/sciimmunol.adk4841
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Fonds De La Recherche Scientifique - FNRS
- Walloon excellence in life sciences and biotechnology
- National Institutes of Health
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé