Quantifying in situ adaptive immune cell cognate interactions in humans

Vladimir M. Liarski, Adam Sibley, Nicholas J. Van Panhuys, Junting Ai, Anthony Chang, Domenick Kennedy, Maria Merolle, Ronald N. Germain, Maryellen L. Giger, Marcus R. Clark

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Two-photon excitation microscopy (TPEM) has revolutionized the understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. The recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. We postulated that by capturing these features in fixed tissue samples, we could quantify in situ adaptive immunity. Therefore, we used a deep convolutional neural network to identify fundamental distance and cell-shape features associated with cognate help (cell-distance mapping (CDM)). In mice, CDM was comparable to TPEM in discriminating cognate T cell–dendritic cell (DC) interactions from non-cognate T cell–DC interactions. In human lupus nephritis, CDM confirmed that myeloid DCs present antigen to CD4 + T cells and identified plasmacytoid DCs as an important antigen-presenting cell. These data reveal a new approach with which to study human in situ adaptive immunity broadly applicable to autoimmunity, infection, and cancer.

Original languageEnglish
JournalNature Immunology
DOIs
Publication statusPublished - 1 Jan 2019

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Cell Communication
Adaptive Immunity
Photons
Microscopy
Cell Shape
T-Lymphocytes
CD4 Antigens
Lupus Nephritis
Antigen-Presenting Cells
Autoimmunity
Animal Models
Antigens
Infection
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Quantifying in situ adaptive immune cell cognate interactions in humans. / Liarski, Vladimir M.; Sibley, Adam; Van Panhuys, Nicholas J.; Ai, Junting; Chang, Anthony; Kennedy, Domenick; Merolle, Maria; Germain, Ronald N.; Giger, Maryellen L.; Clark, Marcus R.

In: Nature Immunology, 01.01.2019.

Research output: Contribution to journalArticle

Liarski, VM, Sibley, A, Van Panhuys, NJ, Ai, J, Chang, A, Kennedy, D, Merolle, M, Germain, RN, Giger, ML & Clark, MR 2019, 'Quantifying in situ adaptive immune cell cognate interactions in humans', Nature Immunology. https://doi.org/10.1038/s41590-019-0315-3
Liarski, Vladimir M. ; Sibley, Adam ; Van Panhuys, Nicholas J. ; Ai, Junting ; Chang, Anthony ; Kennedy, Domenick ; Merolle, Maria ; Germain, Ronald N. ; Giger, Maryellen L. ; Clark, Marcus R. / Quantifying in situ adaptive immune cell cognate interactions in humans. In: Nature Immunology. 2019.
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