Innate cells sense and respond to pathogens, tissue damage and stress by producing pro-inflammatory cytokines and chemokines (PICC), which are physiological steps to mobilize immune defense, tissue repair and restoration of homeostasis. Abnormal inflammatory reponses lead to autoimmunity, fibrosis and other autoinflammatory diseases. Thus inflammatory response is tightly controlled both locally and systemically.

We have previously shown that T cells are both necessary and sufficient to temper Toll like receptor (TLR) mediated inflammatory response to pathogens, in a TCR-independent manner. TCR-independency thus highlights that T cells may possess evolutionally conserved characteristics of innate immune cells. Herein I will also discuss another feature of how pro-inflammatory CD8+ T cells activate macrophages to initiate myocardiac injury casued by hypertension. Macrophages infiltration and activation in myocardium is a pivotal immunopathological lead to hypertensive cardiac micro-injury, but underlying mechanisms remain elusive. We have found that CD8+ T cells are essential for the process. CD8 gene targeting (CD8 KO) or CD8+ T cells depletion by antibody significantly reduced cardiac pro-fibrotic inflammatory responses induced by angiotensin II (Ang II) infusion, whereas CD8 KO mice reconstituted with CD8+ T cells became sensitive to Ang II. More importantly, CD8+ T cells were required for macrophage infiltration in myocardium and subsequent activation to express PICC. Furthermore, macrophage activation required direct contact with CD8+ T cells, but independent of T cell receptor (TCR), both in vitro and in vivo. Finally, hypertension may casue myocardium or myofibroblast cells to produce IFNγ, which is responsible to chemoattract CD8+ T cells to the left ventricles in the onset of cardiac inflammation. Thus, TCR independent innate nature of CD8+ T cells are both necessary and sufficient to induce hypertensive cardiac inflammation.

In conclusion, innate cells, conventional and non-conventional, seem to be both sensors and effectors that determine the magnitude and duration of inflammatory response to tissue damage.