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Quantitative Cell Distance Mapping In Human Nephritis Reveals Organization Of In Situ Adaptive Immune Responses

Clark, Marcus R. MD
Liarski, Vladimir M. MD; Kavernia, Natalya ; Giger, Maryellen L. PhD; Chang, Anthony MD; Peng, Yahui PhD; Brandt, Daniel F. MD
Sunday, October 27, 2013
5:45 PM
Hilton - Indigo C
Session Title:
Systemic Lupus Erythematosus - Human Etiology and Pathogenesis I
Abstract Category:
Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Background/Purpose: Inflammatory infiltrates contain multiple cell types that could interact in myriad ways to amplify in situ immune responses. However, there currently are no methods available to quantitatively assess such interactions in human tissue.

Methods: Therefore, we developed a novel computational approach which we term cell distance mapping (CDM) that, when coupled to confocal microscopy, enabled us to quantitatively assess the spatial relationships between different cell populations.

Results: When applied to human lupus nephritis (LuN), CDM revealed that T follicular helper (TFH)-like cells commonly infiltrated the renal tubulointerstitium with almost half in cognate pairs with B cells. Furthermore, in the absence of evident germinal center (GCs), the overall spatial organization of B cells and TFH cells in LuN was similar to that observed in tonsil GC light zones. TFH-like cells (CD4+ICOS+PD-1+) were also observed in T cell-mediated renal transplant rejection (TCMR) cases. However, the TFH-like cells in TCMR infrequently formed cognate pairs with B cells. Furthermore, the TCMR TFH-like cells did not organize the B cells around them. Finally, while IL-21 expression was high in tonsil GC and LuN TFH-like cells, it was barely detectable in the TFH-like cells infiltrating the tubulointerstitium in TCMR.

Conclusion: These results suggest that even in areas of diffuse inflammation, CDM reveals cellular organizations and inter-cell interactions associated with in situ adaptive immunity. Furthermore, we propose that CDM can discriminate between functional and non-functional TFH cells in situ.


M. R. Clark, None; V. M. Liarski, None; N. Kavernia, None; M. L. Giger, None; A. Chang, Pfizer Inc, 2; Y. Peng, None; D. F. Brandt, None.