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Updated: May 31, 2026

In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
FcγRIIIa (CD16) induction on human T lymphocytes and CD16pos T-lymphocyte amplification
Béatrice Clémenceau1, Régine Vivien, Emilie Debeaupuis
1Institut de Recherche Thérapeutique de l'Université de Nantes, INSERM, U892, France. beatrice.clemenceau@nantes.inserm.fr
Insights
Natural killer (NK) cell stimulation protocols can expand a subset of T lymphocytes expressing the CD16 receptor. This finding suggests a new way to enhance antibody-dependent cellular cytotoxicity in patients.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Natural killer (NK) cells are crucial for innate immunity.
- Standard in vitro methods aim to amplify NK cells using specific cell lines and cytokines.
- Human immunodeficiency virus (HIV) infection impacts immune cell populations.
Purpose of the Study:
- To investigate the T-cell populations generated during NK cell amplification protocols.
- To characterize the phenotype and function of expanded T lymphocytes.
- To explore potential therapeutic applications for enhancing cellular cytotoxicity.
Main Methods:
- Stimulation of peripheral blood mononuclear cells (PBMCs) from HIV+ patients, cord blood, and healthy donors with Epstein-Barr virus-infected B lymphoblastic cell line and interleukin-2 for 2 weeks.
- Flow cytometry analysis to identify T lymphocyte subsets, including CD3, CD16, and αβ T-cell receptor (TCR) expression.
- Cell-sorting experiments and antibody-dependent cellular cytotoxicity (ADCC) assays to assess CD16 receptor function on T lymphocytes.
Main Results:
- NK cell amplification protocols resulted in a significant recovery of CD3CD16 T lymphocytes, with a high percentage expressing αβ TCR.
- The expansion of αβ TCR CD16 T lymphocytes varied across different starting cell populations (cord blood, healthy donors, HIV+ patients).
- Functional CD16 receptors were induced on the surface of αβ TCR CD16 T lymphocytes, indicating potential for ADCC.
Conclusions:
- Standard NK cell amplification protocols can inadvertently expand a specific subset of T lymphocytes.
- These expanded T lymphocytes possess a functional CD16 receptor, suggesting a role in ADCC.
- This finding opens possibilities for enhancing a patient's ADCC potential by targeting this T-cell memory compartment.
Abstract:
During serial assays designed to amplify natural killer (NK) cells in vitro, we observed that when peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus positive (HIV+) patients were stimulated for 2 weeks with an Epstein-Barr virus-infected B lymphoblastic cell line and interleukin-2, a well known procedure to amplify NK cells in vitro, 44.4 ± 18% CD3CD16 T lymphocytes were recovered together with NK cells, of which 78.2% expressed an αβ T-cell receptor (TCR). To identify the T-cell compartment from which they originated (naive, antigen experienced, CD16, or CD16), we first compared the results obtained with HIV+ patients' PBMCs (where essentially all CD8 cells are antigen experienced) with those obtained from cord blood lymphocytes (essentially naive) and PBMC from healthy donors (with variable antigen experience). Two weeks after stimulation, αβ TCR CD16 T lymphocytes increased from 0.3%, 2.2%, and 8.2% to 2.5%, 7.7%, and 36.3%, for cord blood, healthy donors, and HIV+ patients, respectively. Second, using cell-sorting experiments for CD16 cells and antibody-dependent cellular cytotoxicity assays, we demonstrated that a functional CD16 receptor could also be induced at the cell surface of αβ TCR CD16 T lymphocytes. Together, these results demonstrate that under stimulation conditions known to induce NK cell proliferation, a subset of αβ TCR CD16 T cells arises from antigen-experienced CD16 cells but also from antigen-experienced CD16 T lymphocytes, revealing the possibility to increase a patient's antibody-dependent cellular cytotoxicity potential through simple stimulation of this particular memory compartment.

