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Elife. 2019 Jun 25;8. pii: e46045. doi: 10.7554/eLife.46045.

Circulating T cell-monocyte complexes are markers of immune perturbations.

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, United States.
2
Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, United States.
3
Bioinformatics core, La Jolla Institute for Immunology, La Jolla, United States.
4
Department of Zoology and Environment Sciences, Science Faculty, University of Colombo, Colombo, Sri Lanka.
5
North Colombo Teaching Hospital, Ragama, Sri Lanka.
6
National Institute of Infectious Diseases, Gothatuwa, Sri Lanka.
7
National Tuberculosis Reference Laboratory, Welisara, Sri Lanka.
8
National Hospital for Respiratory Diseases, Welisara, Sri Lanka.
9
Genetech Research Institute, Colombo, Sri Lanka.
10
Johns Hopkins School of Public Health, Baltimore, United States.
11
Universidad Peruana Cayetano Heredia, Lima, Peru.
12
Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.
13
Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, United States.
14
Department of Bioengineering, University of California, San Diego, La Jolla, United States.
15
Department of Medicine, University of California, San Diego, La Jolla, United States.

Abstract

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.

KEYWORDS:

cell interactions; flow cytometry; human; immune biomarker; immunology; infectious diseases; inflammation

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