| In the mid 80-ies the concept that atherosclerosis was an inflammatory disease had received general recognition. The artery wall was like a battle field continuously attacked by viscous oxidized LDL and vigorously defended by cells belonging to the innate immune defense system. The innate immune defense is the rapid attack force of the immune system. It consists of alarm-signaling endothelial cells, macrophages and other white blood cells, pro-inflammatory signaling molecules called cytokines and missile-like proteins called complement that can perforate foreign cellular invaders. The innate immune system can act quickly and with considerable strength, but the specificity is poor. Accordingly, being continuously defended by the innate immune system comes with a price for any tissue. For the artery wall this price is destruction of normal tissue structure, chronic inflammation, fibrosis and ulceration. Although this concept appeared to provide a reasonable explanation to development of atherosclerosis reports began to emerge indicating that the biological mechanisms involved in the disease was much more complex. A Swedish research group led by Göran K. Hansson found that atherosclerotic plaques contained activated T cells. This was an observation of considerable importance because these cells are key players in another part of the immune system, the adaptive immunity. The adaptive immune system has a considerably higher degree of specificity and sophistication than the innate immune system, but because of this it also takes a much longer time to activate. Whereas the innate immune cells attack common structural patterns recognized as foreign the T cell only recognize only one specific structure (antigen) and act specifically on that. Because of this millions of T cells with different specificity circulate in the blood and inhabit the different lymphatic organs of the body. Antigens are generally presented to T cells by specialized antigen-presenting cells, macrophages and so called dendritic cells being the most common ones. When T cells encounter their specific antigen they become activated and begin to multiply. Depending on the circumstance of the presentation the T cells may mature into pro-inflammatory attack cells (Th1 cells), cells that dampens inflammation and stimulate antibody production (Th2 cells) or cells that cells that mediate induction of tolerance against the antigen (Treg cells) (figure 3). The observation of activated T cells in atherosclerotic plaques triggered several new intriguing questions. What function did they have in the plaque? Did they promote or inhibit inflammation? Was atherosclerosis an autoimmune disease activated by an adaptive immune response against an antigen in the artery wall? Most of the available evidence suggested that pro-inflammatory cells dominated the atherosclerotic process and experimental animals lacking functional T cells or different pro-inflammatory cytokines exhibit various degree of resistance against development of atherosclerosis. However, the most important challenge was still to find the plaque antigen recognized by the T cells? Infectious microorganisms represented one obvious class of candidates. Could it be that bacteria or viruses infected the vascular wall and that the combined attack of the immune system against both lipids and microorganisms had deleterious effects? It could soon be reported that several types of infectious microorganisms could be detected in plaques and that antibody levels against some of these, primarily one called Chlamydia pneumoniae, were increased in subjects suffering from cardiovascular disease. |
