Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects.
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.
Laboratory of Immunovivology, Clinic Unit of Infectious Diseases, Microbiology and preventive Medicine of Seville, IBiS, Virgen del Rocion University Hospital/CSiC/University of Seville, Seville 41013, Spain.
G
G
Méndez-Lagares
L
L
Díaz
R
R
Correa-Rocha
J A
JA
León Leal
S
S
Ferrando-Martínez
E
E
Ruiz-Mateos
M M
MM
Pozo-Balado
M D
MD
Gurbindo
M I
MI
de José
M A
MA
Muñoz-Fernández
M
M
Leal
Y M
YM
Pacheco
D000293:Adolescent; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016922:Cellular Senescence / Q000276:immunology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load