Profiling calcium signals of in vitro polarized human effector CD4+ T cells

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1865; no. 6; pp. 932 - 943
• Main Authors: Kircher, Sarah, Merino-Wong, Maylin, Niemeyer, Barbara A., Alansary, Dalia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2018
• Subjects: Calcium Signaling - immunology; Cell Differentiation - immunology; Human T cell subtypes; Humans; In vitro polarization; Orai; ORAI2 Protein - immunology; Regulatory T cells; SOCE; Stim; T-Lymphocytes, Helper-Inducer - immunology; SOCE; Stim; Human T cell subtypes; Regulatory T cells; Orai; In vitro polarization
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2018.04.001

Differentiation of naïve CD4+ T cells into effector subtypes with distinct cytokine profiles and physiological roles is a tightly regulated process, the imbalance of which can lead to an inadequate immune response or autoimmune disease. The crucial role of Ca2+ signals, mainly mediated by the store operated Ca2+ entry (SOCE) in shaping the immune response is well described. However, it is unclear if human effector CD4+ T cell subsets show differential Ca2+ signatures in response to different stimulation methods. Herein, we provide optimized in vitro culture conditions for polarization of human CD4+ effector T cells and characterize their SOCE following both pharmacological store depletion and direct T-cell receptor (TCR) activation. Moreover, we measured whole cell Ca2+ release activated Ca2+ currents (ICRAC) and investigated whether the observed differences correlate to the expression of CRAC genes. Our results show that Ca2+ profiles of helper CD4+ Th1, Th2 and Th17 are distinct and in part shaped by the intensity of stimulation. Regulatory T cells (Treg) are unique being the subtype with the most prominent SOCE response. Analysis of in vivo differentiated Treg unraveled the role of differential expression of ORAI2 in fine-tuning signals in Treg vs. conventional CD4+ T cells.
[Display omitted]
•Human CD4+ T cell subtypes have distinct Ca2+ signatures.•In vitro polarization mimics in vivo differentiation.•Regulatory T cells express less Orai2 and exhibit most prominent Ca2+ response.•Ca2+ signatures of CD4+ T cell subtypes are not solely dependent on CRAC genes.