Abstract 4141673: Immunologic Insights: Activated and Exhausted Circulating T-Cell Phenotype in Hypoplastic Left Heart Syndrome (HLHS)

Background: While staged surgical palliation for infants born with hypoplastic left heart syndrome (HLHS) has enabled many patients to survive a previously fatal condition, there is now a growing population of HLHS children and young adults who experience significant co-morbidities and mortality secondary to their palliated physiology. Abnormalities of the immune system, including T-cell lymphopenia, have been documented in HLHS patients. However, the impact of altered T-cell homeostasis remains ill-defined. Hypothesis: Both intrinsic and acquired alterations in T-cell sub-populations results in T-cell activation/exhaustion and a pro-inflammatory phenotype. Methods: Peripheral T-cell sub-populations and activation/inhibition markers were quantified in HLHS (n=32, median age 1.65 years, range 0-13.2 years) and healthy, pediatric controls (n=14, median age 4.55 years, range 0.2-15.1 years) by mass cytometry (Helios Cytometry Time Of Flight, CyTOF). Comparison between HLHS and controls was performed by unpaired t-test or Mann-Whitney, based on normality. Results: In HLHS subjects, circulating CD4 + and CD8 + populations are significantly decreased (p<0.001) compared to control. The proportions of CD4 + HLA-DR + (p<0.05) and CD8 + EOMES + (p<0.01) T cells are increased in HLHS. HLHS CD8 + TC1 + populations are increased (p<0.05) while HLHS CD8 + TC2 + (p<0.05) populations are decreased compared to controls. Notably, there is an increase in CD4 + regulatory T cells in HLHS subjects (p<0.001). Conclusions: Immunoprofiling of peripheral T-cell populations suggests that abnormalities extend beyond a decrease in T-cell numbers: HLHS T cells demonstrate an activated and exhausted phenotype, which may impact development of co-morbidities in this population. Additional investigations are required to delineate the functional consequences of this unique HLHS immunophenotype.