Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects

• Published in: Clinical microbiology and infection Vol. 19; no. 6; pp. 558 - 565
• Main Authors: Méndez-Lagares, G., Díaz, L., Correa-Rocha, R., León Leal, J.A., Ferrando-Martínez, S., Ruiz-Mateos, E., Pozo-Balado, M.M., Gurbindo, M.D., de José, M.I., Muñoz-Fernández, M.A., Leal, M., Pacheco, Y.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier Ltd 01.06.2013; Blackwell Publishing Ltd; Elsevier Limited
• Subjects: Adolescent; Antiretroviral drugs; CD4 Lymphocyte Count; CD4 T cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cellular Senescence - immunology; Child; Cross-Sectional Studies; Drug therapy; Female; HIV; HIV Infections - immunology; HIV Infections - transmission; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Humans; immune reconstitution; Immunologic Memory; Immunophenotyping; immunosenescence; Infectious Disease Transmission, Vertical; Lymphocyte Activation - immunology; Lymphocytes; Male; Phenotype; Senescence; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; vertically HIV-infected subjects; Viral Load; human immunodeficiency virus; immune reconstitution; immunosenescence; CD4 T cells; vertically HIV-infected subjects
• ISSN: 1198-743X; 1469-0691
• DOI: 10.1111/j.1469-0691.2012.03934.x

Vertical transmission of human immunodeficiency virus (HIV) represents an important world-wide health problem although the incidence in developed countries has been drastically reduced by the extensive use of highly active antiretroviral therapy. Vertically HIV-infected subjects have been exposed to the virus during the maturation of their immune systems and have suffered a persistent chronic activation throughout their lifetime; the consequences of this situation for their immune system are not fully understood. The objective of this study was to analyse immunosenescence-related parameters in different CD4 T-cell subsets. Fifty-seven vertically HIV-infected subjects and 32 age-matched healthy subjects were studied. Activation (HLA– DR+), senescence (CD28– CD57+) and proliferation (Ki67+) were analysed on different CD4 T-cell subsets: naive (CD45RA+ CD27+), memory (CD45RO+ CD27+), effector memory (CD45RO+ CD27–) and effector memory RA (CD45RA+ CD27–). Compared with healthy subjects, vertically HIV-infected subjects showed increased naive and memory CD4 T-cell frequencies (p 0.035 and p 0.010, respectively) but similar frequencies of both effector subsets. Whereas naive CD4 T cells were not further altered, memory CD4 T cells presented increased levels of senescence and proliferation markers (p <0.001), effector memory CD4 T cells presented increased levels of activation, senescence and proliferation markers (p <0.001) and effector memory RA CD4 T cells presented increased levels of activation and senescence (p <0.001) compared with healthy subjects. Despite long periods of infection, vertically HIV-infected subjects show specific patterns of immunosenescence, revealing a preserved CD4 T-cell homeostasis for subset differentiation and distribution. Nevertheless, excepting the naive subpopulation, all subsets experienced some immunosenescence, pointing to uncertain consequences of the future aging process in these subjects.