Elsevier

Autoimmunity Reviews

Volume 5, Issue 2, February 2006, Pages 136-139
Autoimmunity Reviews

Aging of the immune system: A risk factor for autoimmunity?

https://doi.org/10.1016/j.autrev.2005.09.008Get rights and content

Abstract

Aging of the immune system, or immunosenescence, is characterized by changes in T cell subsets, cellular and molecular level alterations and thymic atrophy, resulting in a decline of T and B cell function. These alterations have been shown to be accompanied by a loss of ability to recognize “self” and “foreign” antigens. Therefore the development of autoimmune responses like production of autoantibodies has been hypothesized to be secondary to thymus involution with a decline of naïve T cells and accumulation of clonal T cells with activation due to “neoantigens” during the aging process. Altered apoptosis and altered T cell homeostasis have been emphasized to promote a chronic inflammatory state and lead to the concept of a immune-risk phenotype. However, it has to be proven which kinds of mechanisms turn the immune system to manifest autoimmune disease and how speculated defects in T cell differentiation and interaction leading to premature aging of the immune system may contribute to the development of autoimmune diseases.

Introduction

The aging process is a phenomenon that affects every human being as well as all members of animals and plants. Loss of features of young individuals may lead to disabilities in the elderly, on the other hand characteristics being of advantage in young individuals can be of disadvantage in later life. Biological aging processes have been described by several theories. Aging has been discussed as a result of damage due to the influence of free radicals, glycosylation as well as intrinsic and extrinsic factors causing DNA malfunctions. Other theories are based on the assumption of genetic determination of aging resulting in a limited number of possible cell divisions depending of the age of the donor. Changes in cell cycle control and telomere shortening lead to the cessation of replication in senescent cells [1].

A major aspect of individual human aging is the decline of immune function in the elderly resulting in a loss of the ability of the recognition of “self” and “foreign” antigens. It has been hypothesized that secondary to thymus involution with a decline in naïve T cells and the accumulation of memory T cells with activation owing to “neoantigens” during the aging process may cause the development of autoimmune conditions. Diminished apoptosis and altered T cell homeostasis may contribute to a chronic inflammatory state [2].

The following discussion will focus on the features of immunosenescence in autoimmune conditions and on possible links to etiology of the diseases.

Section snippets

Immunosenescence

The aging of the immune system, or immunosenescence, is manifested by an increased susceptibility to infections with increased morbidity and mortality. The most impressive change is the involution of the thymus, starting soon after puberty with decreasing size of the organ progressively with age and resulting in a replacement of thymic tissue by fat [3]. As shown in murine models, thymic atrophy has been reported to be partially due to the failure of thymic T cells to undergo differentiation

Autoimmunity and immunosenescence

Incidence of autoimmune disorders appears to be higher in older humans, although they show a decline in their immunological response to antigenic stimulus with age. Characteristics of the aged immune system are decreasing naïve T cell rates, accumulation of memory cells and a shift from Th1 to Th2 cytokine profiles. In the elderly, there are also higher levels of autoantibodies without clinical relevance, because their numbers are kept low by tolerance mechanisms. The shift to Th2 cytokines has

Conclusion

However, taken together the described observations and recent studies do not lead to a satisfactory answer, which kind of mechanisms turns the immune system to manifest autoimmune disease and how defects in T cell differentiation and interaction leading to premature aging of the immune system may contribute to the development of autoimmune diseases. Concepts of an immune-risk phenotype and alterations of the T cell homeostasis by a chronic inflammatory state and clonal expansions e.g. caused by

References (28)

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