Impact of aging, cytomegalovirus infection, and long-term treatment for human immunodeficiency virus on CD8+ T-Cell subsets

Ellen Veel, Liset Westera, Rogier van Gent, Louis Bont, Sigrid Otto, Bram Ruijsink, Huib H. Rabouw, Tania Mudrikova, Annemarie Wensing, Andy I.M. Hoepelman, José A.M. Borghans, Kiki Tesselaar

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

4 Citaten (Scopus)

Samenvatting

Both healthy aging and human immunodeficiency virus (HIV) infection lead to a progressive decline in naive CD8+ T-cell numbers and expansion of the CD8+ T-cell memory and effector compartments. HIV infection is therefore often considered a condition of premature aging. Total CD8+ T-cell numbers of HIV-infected individuals typically stay increased even after long-term (LT) combination antiretroviral treatment (cART), which is associated with an increased risk of non-AIDS morbidity and mortality. The causes of these persistent changes in the CD8+ T-cell pool remain debated. Here, we studied the impact of age, CMV infection, and LT successful cART on absolute cell numbers in different CD8+ T-cell subsets. While naïve CD8+ T-cell numbers in cART-treated individuals (N = 38) increased to healthy levels, central memory (CM), effector memory (EM), and effector CD8+ T-cell numbers remained higher than in (unselected) age-matched healthy controls (N = 107). Longitudinal analysis in a subset of patients showed that cART did result in a loss of memory CD8+ T-cells, mainly during the first year of cART, after which memory cell numbers remained relatively stable. As CMV infection is known to increase CD8+ T-cell numbers in healthy individuals, we studied whether any of the persistent changes in the CD8+ T-cell pools of cART-treated patients could be a direct reflection of the high CMV prevalence among HIV-infected individuals. We found that EM and effector CD8+ T-cell numbers in CMV+ healthy individuals (N = 87) were significantly higher than in CMV- (N = 170) healthy individuals. As a result, EM and effector CD8+ T-cell numbers in successfully cART-treated HIV-infected individuals did not deviate significantly from those of age-matched CMV+ healthy controls (N = 39). By contrast, CM T-cell numbers were quite similar in CMV+ and CMV- healthy individuals across all ages. The LT expansion of the CM CD8+ T-cell pool in cART-treated individuals could thus not be attributed directly to CMV and was also not related to residual HIV RNA or to the presence of HIV-specific CM T-cells. It remains to be investigated why the CM CD8+ T-cell subset shows seemingly irreversible changes despite years of effective treatment.

Originele taal-2Engels
Artikelnummer572
TijdschriftFrontiers in Immunology
Volume9
Nummer van het tijdschriftMAR
DOI's
StatusGepubliceerd - 21 mrt. 2018
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'Impact of aging, cytomegalovirus infection, and long-term treatment for human immunodeficiency virus on CD8+ T-Cell subsets'. Samen vormen ze een unieke vingerafdruk.

Citeer dit