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In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8؉ T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8 ؉ T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naïve (CD45RA ؉ CD28 ؉ ), memory (CD45RA ؊ CD28 ؉ ), and effector (CD45RA؉ T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65 495-503 -specific CD8 ؉ T cells were also studied. We demonstrate that aging as well as CMV infection lead to a decrease in the size of the naïve CD8 ؉ T-cell pool but to an increase in the number of CD8؉ effector T cells, which produce gamma interferon but lack substantial growth potential. The size of the CD8 ؉ memory T-cell population, which grows well and produces interleukin-2 (IL-2) and IL-4, also increases with aging, but this increase is missing in CMV carriers. Life-long latent CMV infection seems thus to diminish the size of the naïve and the early memory T-cell pool and to drive a Th1 polarization within the immune system. This can lead to a reduced diversity of CD8 responses and to chronic inflammatory processes which may be the basis of severe health problems in elderly persons.

Abstract-Hallmarks of inflammation in various cardiovascular diseases, notably atherosclerosis, have been observed for a long time. However, evidence for an (auto)antigen-driven process at these sites of inflammation has come forward only recently. Heat shock proteins (HSPs) have been identified as playing either immunologically mediated disease promoting or protective roles. HSP60 has been shown to trigger innate and adaptive immune responses that initiate the earliest still reversible inflammatory stage of atherosclerosis. HSP60 is structurally highly conserved and abundantly expressed by prokaryotic and eukaryotic cells under stressful conditions. Beneficial protective immunity to microbial HSP60 acquired by infection or vaccination and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. In vitro and in vivo experiments have demonstrated that classical atherosclerosis risk factors can act as endothelial stressors that provoke the simultaneous expression of adhesion molecules and of HSP60 in mitochondria, in cytoplasm, and on the cell surface, where it acts as a "danger signal" for cellular and humoral immune reactions. Hence, protective, preexisting anti-HSP60 immunity may have to be "paid for" by harmful (auto)immune cross-reactive attack on arterial endothelial cells maltreated by atherosclerosis risk factors. These experimentally and clinically proven findings are the basis for the autoimmune concept of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:960-968.)Key Words: atherosclerosis Ⅲ endothelium Ⅲ immune system Ⅲ risk factors Ⅲ stress Ⅲ heat shock protein T ypical cellular hallmarks of chronic inflammation and infections, notably infiltration by mononuclear cells, are also present in the cardiovascular system, as has been known for more than 150 years. However, until quite recently, it was not clear whether these inflammatory immunologic processes are primary or secondary in nature. 1 One of the reasons for this uncertainty may have been the fact that most investigations in humans were conducted on surgical or autopsy specimens representing very advanced stages of cardiovascular disease (CVD) and thus did not provide information on the initial mechanisms triggering these processes. In complex situations, such as in atherosclerosis, it was also difficult to appreciate that different, clinically well-proven risk factors may provoke a similar, or even identical, pathophysiological outcome. The main thrust to resolve this dilemma was to delineate the array of nonspecific and specific humoral and cellular inflammatory reactions taking place within the afflicted vascular territories. The availability of animal models that, at least partly, mimic human CVD was of utmost importance for this progress. In recent decades, the aim has been to identify exogenous or autologous antigens that may induce the local cardiovascular immune reactions. Among the candidates for such antigens are infectious agents, such as Chlamydia pneumoniae, as well as autoantigens, such as b...

The authors' results indicate that silicone implants trigger a specific, antigen-driven local immune response through activated TH1/TH17 cells, suggesting that ensuing fibrosis is promoted by the production of profibrotic cytokines as a consequence of faltering function of local T regulatory cells.