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Specific Patterns of T Cell Immunosenescence in Vertically HIV-Infected Subjects

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Handbook of Immunosenescence

Abstract

The immunosenescence process that occurs during aging involves serious changes on T cell subsets that compromise the functionality of the adaptive immune responses and may impact the clinical evolution of the elderly population. HIV-infection is considered a model of premature immunosenescence, and its related T cell changes are being associated to the development of non-AIDS related (aging-related) clinical events and the risk of death of the chronic HIV-infected subjects. Vertical HIV-infection has relevant peculiarities mainly because HIV-infection occurs during the maturation of immune system, when a high thymic function and an actively dividing T cell population (accompanying somatic growth) are present. There are evidences that vertically HIV-infected subjects start showing signs of T cell immunosenescence with marked alterations in the cellular subsets distribution and expression of markers of senescence, activation, proliferation, and exhaustion. CD8 T cell subsets are seriously affected by HIV-infection, highly aggravated by the presence of detectable viral load levels, whereas CD4 subsets seem to be more preserved. Treg cells could play a beneficial role in controlling T cell immunosenescence but such function could rely on the viral load suppression. Evidences highly stress the need for early and long-standing control of HIV replication in vertically HIV-infected children and young. Whether T cell immunosenescence could affect the development of age-related diseases in this scenario is still unknown, but HIV-infected children already show structural changes of the vasculature, measured by the carotid intima media thickness (IMT) and metabolic alterations, that could reflect the subjacent premature development of cardiovascular manifestations.

Funding: Y. M. Pacheco was supported by the Fondo de Investigación Sanitaria through the “Miguel Servet” program [CPII13/00037] and by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the “Nicolás Monardes” program [C-0010/13]. E. Ruiz-Mateos was supported by the Fondo de Investigación Sanitaria through the “Miguel Servet” program [CPII14/0025]. This work has been partially funded by the Spanish AIDS Research Network of Excellence [RIS; RD12/0017/0029, RD12/0017/0037].

Author contribution: YMP and ML drafted the text. YMP wrote the text. All the authors critically revised the text.

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Abbreviations

cART:

Combined anti-retroviral therapy

HIV:

Human immunodeficiency virus

PBMC:

Peripheral blood mononuclear cells

RTE:

Recent thymic emigrant

TCR:

T cell receptor

TemRA:

Terminally differentiated effector memory CD45RA+

Treg cells:

Regulatory T cells

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Pacheco, Y.M., Méndez-Lagares, G., Ruiz-Mateos, E., Muñoz-Fernández, M.Á., Leal, M. (2019). Specific Patterns of T Cell Immunosenescence in Vertically HIV-Infected Subjects. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-99375-1_133

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