Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulation.
OBJECTIVE
To analyse the role of thymic function and its association with cellular immunosenescence markers in patients with low-level CD4 T cell repopulation, despite complete HIV RNA replication control on highly active antiretroviral therapy (HAART).


METHODS
Cellular immunosenescence markers comparing patients with CD4 T cell counts <or=250 cells/mm(3) for >or=48 weeks (n = 11) and patients with a CD4 T cell count >or=500 cells/mm(3) (n = 11) were investigated. Both groups were also compared with 11 healthy volunteers of similar age. Naive CD4 T cell counts, beta- and delta-T cell rearrangement excision circles, recent thymic emigrants, replicative senescence marker, cell activation, and rate of apoptosis were analysed. The Mann-Whitney U-test was used to compare parameters between both low-level and high-level CD4 T cell repopulation groups, and healthy volunteers.


RESULTS
Our results showed a lower thymic activity in patients with low-level CD4 T cell repopulation, leading to a decline in CD4 T cell production. On the other hand, a higher activation along with a higher replicative senescence of CD4 T cells contributed to a higher rate of apoptotic CD4 T cells in this group of patients.


CONCLUSIONS
We propose a model with several different related mechanisms involved in premature immune senescence in HIV-infected patients with low-level CD4 repopulation on HAART. The understanding of such different mechanisms could help find effective strategies to prevent immune decay.
Molina-Pinelo
Sonia
S
Laboratory of Inmunovirology, Service of Infectious Diseases, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla, Sevilla, Spain.
Vallejo
Alejandro
A
Díaz
Laura
L
Soriano-Sarabia
Natalia
N
Ferrando-Martínez
Sara
S
Resino
Salvador
S
Muñoz-Fernández
María Angeles
MA
Leal
Manuel
M
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology*
D019380:Anti-HIV Agents; D015415:Biomarkers