Background/Purpose:

An atlas of the developing immune system will aid in our understanding of its normal maturation and identification of disease-associated cell subsets. The availability of high dimensional mass cytometry has provided an opportunity for the creation of this reference standard. However, the power available from these big data has not been fully harnessed due to the current focus on specific cell subsets and age groups. There is a critical unmet need for standardized datasets depicting at single cell level and with high dimensionality the entire developmental gradient of the healthy immune system from the neonatal to adult age.

Methods:

To address this need, we constructed an immune atlas from the mass cytometry data obtained from the peripheral blood mononuclear cell samples of 113 healthy individuals (cord blood, newborn to adult) using 63 phenotypical and functional immune markers encompassing the major immune lineages. Quality control check and batch effect correction were done before dimensional reduction and clustering to identify the unique cell subsets. Their frequencies across the age categories were presented as 3-D frequency histograms to create the immune landscape. This database and the analytic pipeline were incorporated into a web portal that allows user to interact as well as upload their own data for comparison.

Results:

Here, we described EPIC with examples of representative immune subsets over the entire age spectrum. There was a distinct segregation of the naive T cell subset enriched in the cord blood/newborn period from the memory T cell subset enriched in adulthood. The naive IL8+ and TNFα+ CD4+ T cells accounted for prominent peaks in the immune landscape during the cord blood/newborn period. In contrast, the memory IFNγ+ and TNFα+ CD4+ T cells were enriched in adulthood.

Transition developmental milestones were observed in the TNFα+ CD4+ T cells where the size of its memory subset would exceed its naive subset at 8 year old. There was a significant reduction and increase in the frequency of the naive and memory TNFα+ CD4+ T cells with a Spearman’s correlation coefficient, rho, of -0.4662 and 0.4164 respectively (both p < 0.0001). A similar intersection was present for the naive and memory regulatory T cell (CD4+, CD25+, Foxp3+, CD152+) subsets at 14 year old with a rho of -0.537 and 0.5034 respectively (both p < 0.0001).

Conclusion:

A holistic description of the developing immunome was obtained with key developmental milestones in the T cell compartment identified. This atlas has the translational potential of aiding the identification of pathologic immune cell subsets in diseases through its comparison with this reference dataset found in the freely available EPIC web portal.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/extended-phenotypic-immunome-characterization-epic-a-web-based-immune-reference-atlas/