Autoantibody-Enhanced, CD32-Driven Trogocytosis Creates Functional Plasticity of Immune Cells and is Hijacked by HIV-1 to Infect Resting CD4 T Cells

Abstract

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here we report that a broad range of surface receptors is transferred in primary cell co-cultures from macrophages to CD4 T cells and identify the Fcg receptor CD32 as driver and cargo of this trogocytotic transfer. Imaging unveiled long filamentous nanoprotrusions that deposit distinct plasma membrane patches from CD32+ donor to target T cells. Transferred receptors conferred cell migration and adhesion properties to recipient cells and macrophage-derived membrane patches rendered resting CD4 T cells susceptible to infection by serving as hotspots for binding and fusion of HIV-1 particles. Importantly, antibodies that recognize epitopes on the surface of T cells markedly enhanced CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies were found in the blood of HIV-1 patients and consistently, the percentage of CD32+ CD4 T cells was increased in their peripheral blood. This Fcg receptor-mediated, antigen-independent cell communication mode transiently expands the functional plasticity of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

Note:
Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (DFG): grant FA378/11-2 (to OTF), grant KE742/4-2 (to OTK), a grant as part of SPP-1923 (to OTK), FOR2830 HE 2526/9-1 (to HH), Ro 25257/-1 grant No. 391217598 and SFB/TR-237-B14 grant No. 369799452 project No. 404450088 (to SR), FG SU1030/1-2 as part of SPP1923 (to KS) and DI714/18-2 (to UD); The Deutsche Zentrum für Infektionsforschung (DZIF): Project TTU 04.820 (to OTK and OTF), project no. TTU 04.710 to VL, and clinical leave fellowship to MM, the China Scholarship Council: Fellowship to QX, LMUexcellent: LMU Research Fellowship to EMP and the Friedrich-Baur-Foundation: Young scientist grant to MA.

Declaration of Interests: The authors declare no competing interests.

Ethical Approval Statement: Human CD4 T cells and CD14+ monocytes were isolated from heparinized blood retained in leukocyte reduction system chambers from healthy blood donors with approval by the Ethics Committee of the Medical Faculty of LMU München (Project No. 17-202 UE).

PBMCs from HIV-1 patients were obtained with informed consent and approval by the local Ethics Committees of the Medical Faculty of LMU München (Project No. 21-0866) and TUM (Project No. 548/21).

Macroscopically normal human jejunum or ileum tissue samples were obtained from patients undergoing elective abdominal surgery. This study has been approved by the Ethics Committee of the Medical Faculty of the University Duisburg-Essen (Project No. 15-6310-BO).

Tonsil tissue was removed during therapeutic tonsillectomy from HIV-, hepatitis B virus-, and hepatitis C virus-negative patients with informed consent. Use of anonymous surgical waste for research was approved by the Ethics Committee of the Medical Faculty of LMU München (Project No. 18-209 UE).

Anonymized human serum samples were obtained from the Diagnostic Department of the Max von Pettenkofer Institute with approval by the local Ethics Committee.

Keywords: immune cell communication, trogocytosis, nanotubes, Fcgamma receptor, HIV reservoir, resting CD4 T cells