TY - JOUR
T1 - Circulating T cell-monocyte complexes are markers of immune perturbations
AU - Burel, Julie G.
AU - Pomaznoy, Mikhail
AU - Arlehamn, Cecilia S.Lindestam
AU - Weiskopf, Daniela
AU - Antunes, Ricardo da Silva
AU - Jung, Yunmin
AU - Babor, Mariana
AU - Schulten, Veronique
AU - Seumois, Gregory
AU - Greenbaum, Jason A.
AU - Premawansa, Sunil
AU - Premawansa, Gayani
AU - Wijewickrama, Ananda
AU - Vidanagama, Dhammika
AU - Gunasena, Bandu
AU - Tippalagama, Rashmi
AU - de Silva, Aruna D.
AU - Gilman, Robert H.
AU - Saito, Mayuko
AU - Taplitz, Randy
AU - Ley, Klaus
AU - Vijayanand, Pandurangan
AU - Sette, Alessandro
AU - Peters, Bjoern
N1 - Funding Information:
We thank Dr Chery Kim and all present and past members at the flow cytometry core facility at the La Jolla Institute for Immunology for assistance in cell sorting and technical discussion. We thank Dr Zbigniew Mikulski from the microscopy core at the La Jolla Institute for Immunology for assistance and technical advice on microscopy imaging. We thank Yoav Altman at the Sanford Burnham Prebys flow cytometry core for technical assistance with imaging flow cytometry. We thank Dr Joe Trotter from the R and D Advanced Technology Group at BD Biosciences for useful technical discussion about cytometry instrument fluidic systems. Research reported in this manuscript was supported by the National Institute of Allergy and Infectious Diseases division of the National Institutes of Health under award number U19AI118626, R01AI137681, HHSN272201400045C, P01HL078784, S10OD021831 and S10OD016262. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Imaging flow cytometry was supported by the James B Pendleton Charitable trust.
Funding Information:
Human subjects: Ethical approval to carry out this work is maintained through the La Jolla Institute for Allergy and Immunology Institutional Review Board (protocols VD-143, VD-085, VD-090), the Medical Faculty of the University of Colombo (which served as a National Institutes of Health-approved institutional review board for Genetech, protocols EC-15-094, EC-15-002, EC.15.095), and the Johns Hopkins School of Public Health Institutional Review Board (RHG holds dual appointment at UPCH and JHU; protocol 00003804). All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki. All participants, except anonymously recruited blood bank donors in Sri Lanka, provided written informed consent prior to participation in the study.
Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.
AB - Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.
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U2 - 10.7554/ELIFE.46045
DO - 10.7554/ELIFE.46045
M3 - Article
C2 - 31237234
AN - SCOPUS:85068748226
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e46045
ER -