Premature Immunosenescence in Rheumatoid Arthritis and Multiple Sclerosis Patients

Abstract

Patients suffering from T cell mediated autoimmune diseases (AIDs) show immune abnormalities that resemble the typical characteristics of immune dysfunction described in the elderly. In addition, the incidence of AIDs increases with advancing age. To evaluate whether rheumatoid arthritis (RA) and multiple sclerosis (MS) patients have suffered from a premature immunosenescence, we measured two indicators of aging. The number of T cell receptor excision circles (TRECs) and the percentage of CD4+CD28 null T cells were studied in peripheral blood mononuclear cells (PBMC) of 60 RA patients, 32 MS patients and 40healthy controls (HC). TREC numbers were decreased in RA and MS patients as compared to age-matched HC indicating premature thymic involution. Moreover, a subset of these patients contained age-inappropriate high frequencies of CD4+CD28 null T cells. This study provides evidence of a premature senescence of the immune system in both RA and MS patients.Premature aging could be a risk factor for developing autoimmunity in genetically prone individuals in a susceptible environment.2

Immunosenescent CD57+CD4+T-cells Accumulate and Contribute to Interferon-γResponses in HIV Patients Responding Stably to ART

“…+ T-cells in the circulation of HIV patients receiv-ing long-term ART is similar to findings in patients with autoimmune diseases, such as rheumatoid disease and multiple sclerosis [8][9][10]. It is hypothesised that continuous immune stimulation expands populations of terminally differentiated effector memory Tcells with characteristics of immunologically senescent T-cells [9], generating premature aging of the immune system.…”

“…Continued T-cell replication accelerates T-cell differentiation in HIV infection [6,7] and other chronic inflammatory diseases [8][9][10]. It is also a feature of normal aging of the immune system [11].…”

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

“…Altogether this may lead to enhanced co-stimulation of CD4 1 CD28 À T cells, which may contribute to pathogenesis of disease [46]. We and others have previously shown that the presence of CD4 1 CD28 À T cells in patients with RA is strongly associated with CMV infection [47,48]. Indeed, a significant proportion of CD4 1 CD28 À T cells display specificity for CMV antigens and a majority of the CMV-specific CD4 1 T cells lack CD28 [47,49].…”

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

“…Important features of accelerated immunosenescence in RA are thymic involution, increased clonal population of T cells in the periphery, decline in the telomere lengths and loss of the CD28 costimulatory receptor [15]. The decline in the generation of new T cells by the thymus has been associated with increased compensatory (homeostatic) proliferation in the periphery.…”