Background and Aims: Preclinical data suggest that activation of the adaptive immune system is critical for myocardial repair processes after ST-elevation myocardial infarction (STEMI). The aim of the present study was to determine the serum kinetics of the effector T-cell chemokine CXCL10/IP-10 in the acute phase of STEMI and its association with left ventricular function recovery and cardiovascular outcomes in patients after STEMI.

Methods: Serum IP-10 levels were retrospectively quantified by ELISA in serum probes derived from two independent cohorts of STEMI patients undergoing primary percutaneous coronary intervention. In the Newcastle cohort (n=47), CMR imaging was obtained with a Siemens Avanto 1.5 Telsa MRI scanner, using a phased array body coil combined with a spine coil at 2-7 days post-reperfusion, and repeat CMR at 12 ± 2 weeks was obtained to assess myocardial function improvement by calculating change in LV ejection fraction (ΔLVEF). A 6-colour assay was used to measure the expression of CD3, CD4, CD8, CD45RA, CCR7 and CX3CR3 in blood samples. T-lymphocytes (CD3+) were first gated into CD4+ and CD8+ T cells, then into four subsets of each by expression of CCR7, the chemokine receptor for CCL19/21, and CD45RA. Four sub-populations of CD4+ and CD8+ T-cells were determined, i.e. naïve (TNaive), central memory (TCM), effector memory (TEM) and terminally differentiated effector memory cells (TEMRA) in peripheral blood on admission, at 5, 15, 30 and 90 minutes, 24 hours and 2 weeks post-reperfusion. In the Newcastle cohort, the primary endpoint of our study was a change in LVEF at 12 weeks post-STEMI versus LVEF at 2-7 days (median: 3 days) post-STEMI (ΔLVEF). Linear regression was used to examine the association of IP-10 levels with ΔLVEF, as a cardiac repair marker, after adjustment for confounders. In the Heidelberg cohort (n=331), the primary endpoint was a composite of all-cause death, myocardial infarction, stroke, resuscitation and revascularisation (percutaneous coronary angiography, coronary artery bypass graft). Cox proportional-hazards models were used to examine the association between IP-10 levels and the primary outcome. 
Results: We report a biphasic response of the effector T cell trafficking chemokine CXCL10/IP-10 characterized by an initial increase of its serum levels in the acute phase of STEMI followed by a rapid reduction already 90min post reperfusion. Patients at the highest IP-10 tertile presented also with more CD4 effector memory (CD4EM) cells, but not other T cell subtypes, in blood. In the Newcastle cohort, patients in the highest IP-10 tertile or CD4EM cells at admission exhibited an improved left ventricle ejection fraction recovery compared to patients in the lowest IP-10 tertile. In the Heidelberg cohort, STEMI patients were followed for a median of 540 days for major adverse cardiovascular events (MACE). Patients presented with a higher serum IP-10 levels at admission had a lower risk for MACE after adjustment for traditional risk factors, CRP and high-sensitivity troponin-T levels (highest vs. rest quarters: HR[95% CI]=0.420 [0.218-0.808]).

Conclusion: Increased serum levels of CXCL10/IP-10 on admission predict left ventricular function recovery and cardiovascular outcomes in patients with STEMI.