Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment

• Published in: Scientific reports Vol. 6; no. 1; p. 34942
• Main Authors: Schrier, Sarah B., Hill, Abby S., Plana, Deborah, Lauffenburger, Douglas A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.10.2016; Nature Publishing Group
• Subjects: 13; 631/250/98; 631/553; 96; 96/106; 96/21; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Communication; Cells, Cultured; Coculture Techniques; Communication; Cytokines; Cytokines - metabolism; Female; Humanities and Social Sciences; Humans; Immunology; Lymphocytes; Lymphocytes T; Male; Monocytes; Monocytes - immunology; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep34942

Physiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors. Computational analysis of the resulting data-sets elucidated communication-independent and communication-dependent contributions, including both positive and negative synergies. We find that cytokines in cell supernatants were uncorrelated to those found in plasma. Additionally, as an example of positive synergy, production levels of CXCR3 cytokines IP-10 and MIG, depend non-linearly on both IFNγ and TNFα levels in cross-talk between T cells and monocytes. Overall, this work demonstrates that communication between cell types can significantly impact the consequent cytokine environment, emphasizing the value of mixed cell population studies.