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Massive CD4+ T-cell depletion as well as sustained immune activation and inflammation are hallmarks of Human Immunodeficiency Virus (HIV)-1 infection. In recent years, an emerging concept draws an intriguing parallel between HIV-1 infection and aging. Indeed, many of the alterations that affect innate and adaptive immune subsets in HIV-infected individuals are reminiscent of the process of immune aging, characteristic of old age. These changes, of which the presumed cause is the systemic immune activation established in patients, likely participate in the immuno-incompetence described with HIV progression. With the success of antiretroviral therapy (ART), HIV-seropositive patients can now live for many years despite chronic viral infection. However, acquired immunodeficiency syndrome (AIDS)-related opportunistic infections have given way to chronic diseases as the leading cause of death since HIV infection. Therefore, the comparison between HIV-1 infected patients and uninfected elderly individuals goes beyond the sole onset of immunosenescence and extends to the deterioration of several physiological functions related to inflammation and systemic aging. In light of this observation, it is interesting to understand the precise link between immune activation and aging in HIV-1 infection to figure out how to best care for people living with HIV (PLWH). [ABSTRACT FROM AUTHOR]

Many of the alterations that affect innate and adaptive immune cell compartments in HIV-infected patients are reminiscent of the process of immune aging, characteristic of old age. These alterations define the immunological age of individuals and are likely to participate to the decline of immune competence with HIV disease progression. It is therefore important to characterize these changes, which point toward the accumulation of highly differentiated immunocompetent cells, associated with overall telomere length shortening, as well as understanding their etiology, especially related to the impact of chronic immune activation. Particular attention should be given to the exhaustion of primary immune resources, including haematopoietic progenitors and naïve cells, which holds the key for effective hematopoiesis and immune response induction, respectively. The alteration of these compartments during HIV infection certainly represents the foundation of the immune parallel with aging. [ABSTRACT FROM AUTHOR]

When encountering foreign antigens, naïve T cells become activated and differentiate into effector and memory T cells. They represent therefore the primary source to mount an immune response against pathogens or tumors. Recent evidence of both quantitative and qualitative alterations of naïve T cells has accumulated in aged mice, indicating that the successful generation of primary T cell responses from the naïve T cell pool may be compromised with old age. However, the vast majority of the data supporting compromised naïve T cell priming efficacy with old age have been produced in animal models, and the situation is much less clear in humans. In the elderly, the involution of the thymus and the associated decline in thymic output result in a decreased number of naïve T cells, which is partially compensated by homeostatic proliferation. Emerging evidence suggest that alterations of the TCR repertoire diversity and intrinsic defects of old CD4+ naïve T cells may impact on their responsiveness to antigenic stimulation. Increasing focus on the study of naïve T cells (in particular CD8+) in old humans are needed to fill the gaps in our understanding of reduced cellular immunity with aging. [ABSTRACT FROM AUTHOR]

The thymus is responsible for the maturation of lymphoid precursors into T cells, and is necessary to establish the T cell pool during prenatal and early postnatal life in humans. With the years, it undergoes a natural shrinking process, referred to as involution, suspected to be central in the decline of immune competence with aging, or immunosenescence. Here, we review the recent studies focusing on the immunological consequences of abnormal thymic development and thymectomy shortly after birth. These works highlight the importance of the thymic function in preserving immune efficacy throughout life, and provide insights into the development of immune aging. [ABSTRACT FROM AUTHOR]

Life expectancy is continuously increasing due to major progress in preventing, delaying or curing various pathologies normally encountered in old age. However, both scientific and medical advances are still required to understand underlying cause of the disparate comorbidities occurrence with aging. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, associated with pro-inflammatory environment. In another hand, stressful events (acute or chronic) can also impact the immune system through the secretion of hormones, which are also altered with aging. The field of psychoneuroimmunology is now providing evidences that in acute medical conditions, elderly people are not equal in their responses to stressors depending on many extrinsic and intrinsic factors. These parameters could interfere with elderly's ability to mount an effective immune response. The objective of this review is to provide an overview of the literature (from fundamental to clinical observations) to draw a parallel between immune dysregulation caused by stress or by aging. Understanding this entanglement could enable us to target fundamental age-related pathways and thus open new avenues in improving both lifespan and health span. [ABSTRACT FROM AUTHOR]

Abstract: A recent consensus has emerged regarding the association between chronic immune activation and poor outcome in HIV-1 infection. However, its basis remains unclear. Accumulating evidence suggests that the cells of the immune system may have a limited replicative lifespan in vivo. In this context, persistent activation during chronic HIV infection may lead to an exhaustion of immune resources. This may occur at two levels: Clonal and Global. Some HIV-1-specific CD8+ T-cells start expressing the senescence marker CD57 soon after primary infection. Persistently activated HIV-1-specific T-cell clones may eventually reach stages of replicative senescence and disappear, resulting in the specific loss of CD8+ T-cell populations important to control viral replication. In addition, HIV-1 infected individuals are characterized by the accumulation of highly differentiated CD8+ and CD4+ T-cells overtime. Together with the decline of T-cell renewal capacities, this may reflect a general ageing of the lymphocyte population. Similar observations have been done in HIV non-infected elderly individuals, which suggests that premature immunosenescence occurs in HIV-1 infection, as a result of persistent immune activation. [Copyright &y& Elsevier]

Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8+ T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8+ T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8+ T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8+ T-cell responses specific for a model antigen. Reduced CD8+ T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8+ T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging. [ABSTRACT FROM AUTHOR]