Quantifying in situ adaptive immune cell cognate interactions in humans

Area of Science:

• Immunology
• Computational Biology
• Pathology

Background:

• Two-photon excitation microscopy (TPEM) advanced adaptive immunity research but is limited to animal models.
• Studying human adaptive immunity in situ is crucial for understanding diseases.

Purpose of the Study:

• To develop a novel method for quantifying in situ human adaptive immunity using fixed tissue samples.
• To establish cell-distance mapping (CDM) as a viable alternative to TPEM for studying T cell-antigen-presenting cell interactions.

Main Methods:

• Utilized a deep convolutional neural network to analyze cell-distance and cell-shape features.
• Developed cell-distance mapping (CDM) to identify cognate T cell-dendritic cell (DC) interactions.
• Validated CDM in mouse models and applied it to human lupus nephritis samples.

Main Results:

• CDM effectively discriminated between cognate and non-cognate T cell-DC interactions in mice, comparable to TPEM.
• In human lupus nephritis, CDM identified myeloid DCs presenting antigens to CD4+ T cells.
• Plasmacytoid DCs were identified as significant antigen-presenting cells in human lupus nephritis.

Conclusions:

• Cell-distance mapping (CDM) provides a novel, broadly applicable approach to study human in situ adaptive immunity.
• CDM can be utilized across various conditions including autoimmunity, infections, and cancer.
• This method facilitates the study of human adaptive immunity without requiring live animal models.