Open Access

Nadine Gladow, Claudia Hollmann, Johannes Weirather, Xin Ding, Matthias Burkard, Sabrina Uehlein, Richa Bharti, Konrad Förstner, Thomas Kerkau, Niklas Beyersdorf, Stefan Frantz, Gustavo Ramos, Ulrich Hofmann

• Myocardial infarction (MI) induces the generation of proinflammatory Ly6C high monocytes in the spleen and the recruitment of these cells to the myocardium. CD4 + Foxp3 + CD25 + T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4 + T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4 + T-cell deficient animals. Conventional CD4 + T-cells promoted myelopoiesis in vitro by cell–cell-contact and paracrine mechanisms, including interferon-gamma (IFN-γ) signalling. Depletion of regulatory T-cells enhanced myelopoiesis in vivo, as evidenced by increases in progenitor cell numbers and proliferative activity in the spleen 5 days after MI. The frequency of CD4 + T-cells-producing factors that promote myelopoiesis increased within the spleen of Treg-depleted mice. Moreover, depletion of Tregs caused a proinflammatory bias in splenic Ly6C high monocytes, which showed predominantly upregulated expression of IFN-γ responsive genes after MI. Our results indicate that conventional CD4 + T-cells promote and Tregs attenuate splenic myelopoiesis and proinflammatory differentiation of monocytes.