Immunosenescent CD8 ⁺ T Cells and C-X-C Chemokine Receptor Type 3 Chemokines Are Increased in Human Hypertension

Abstract

Abstract-The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age-and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8 + T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8 + T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8 + T cells may offer new opportunities for the prevention and treatment of human hypertension. (Hypertension. 2013;62:126-133.)

Spironolactone Decreases DOCA–Salt–Induced Organ Damage by Blocking the Activation of T Helper 17 and the Downregulation of Regulatory T Lymphocytes

“…21 We observed increased CD8 + /IL-17 + cells in DOCA-salt rats, an effect that was prevented by spironolactone ( Figure S3). …”

Significant Association between Serum Monokine Induced by Gamma Interferon and Carotid Intima Media Thickness

“…An antagonist of CXCR3 was also shown to attenuate atherosclerotic plaque formation in low-density lipoprotein receptor-deficient mice by blocking the migration of CXCR3 effector T cells from the peripheral circulation into atherosclerotic lesions 10) . Recent human studies also reported that circulating CXCR3 chemokines are elevated in patients with essential hypertension or aortic aneurysms 11,12) . These data indicate that CXCR3 chemokines may therefore play a role in the development of atherosclerosis.…”

“…Data are presented as the mean SD or n (%). strated that T cell-driven inflammation may be important in the pathogenesis of hypertension and that MIG and IP-10 were significantly elevated in hypertensive subjects 11) . As a result, we sought to extend this finding to demonstrate the association of T cell chemokines with atherosclerosis.…”

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…74 They are characterized by loss of CD28 marker and appearance of CD57 and functionally produce tumor necrosis factor-α and interferon-γ, which affect vascular changes. 75 While early studies have shown that T cells are key in hypertension, 76,77 recent clinical studies indicate that their role is related to a close interaction with other elements of innate, cellular, and humoral immunity. 76 In particular, B cells seem to be essential in hypertension, and their lack is associated with diminished vascular oxidative stress.…”