*Purpose: Quilty lesions (QL) are commonly sub-endocardial lymphoid aggregates found in biopsies from heart transplants. Their appearance and presence in the cardiac tissue is still a mystery, without clear evidence of their relationship with rejection or acceptance of the allograft.

*Methods: 42 heart allograft biopsies from one institution were included in the study. Immunohistochemistry (IHC) was performed for the T-cell markers CD4 and CD8, and the immune regulatory markers Fox-p3 and TGFbeta-1. A sub-set of 9 of these biopsies, 5 with QL and 4 without QL were selected for RNA extraction and gene analysis using the Nanostring n-Counter Human Orghan Transplant Immunology Panel (Seattle, WA).

*Results: Biopsies with TGFbeta-1 (OR 1.4, p<0.05) and Foxp3 (OR 1.3, p<0.05) positive stain in QL were associated with better allograft acceptance. CD4 and CD8 stain in QL were not associated with rejection, however. interstitial CD4+<(p<0.04) and C<8+ (p<0.02) T-cells were associated with rejection.The sub-set of biopsies with QL showed a predominance of adaptive type Th2 response over Th1 genes (3.88x vs. 3.15x). Particular regulatory genes (all p< 0.001) that were higher in biopsies with QL included TGFbeta1, IL10RA, Foxp3 and JAK3. Other pathways analyzed shows anupregulation of genes of cell-extracellular matrix interaction, adaptive immune response, innate immune response, Th17 mediated biology, T-reg differentiation, TGF-beta signaling, TNF family signaling and type I interferon signaling in biopsies with QL (Figure 1)

*Conclusions: Heart allograft biopsies with QL showed a predominance of regulatory signals by both IHC and RNA gene analysis compared to biopsies without QL. QL, far from being passive bystanders, may have an immunomodulatory function in cardiac allografts.

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