Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging.
It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/microl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.
Vrisekoop
Nienke
N
Department of Immunology, University Medical Center, Utrecht, The Netherlands.
van Gent
Rogier
R
de Boer
Anne Bregje
AB
Otto
Sigrid A
SA
Borleffs
Jan C C
JC
Steingrover
Radjin
R
Prins
Jan M
JM
Kuijpers
Taco W
TW
Wolfs
Tom F W
TF
Geelen
Sibyl P M
SP
Vulto
Irma
I
Lansdorp
Peter
P
Tesselaar
Kiki
K
Borghans
José A M
JA
Miedema
Frank
F
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1