Cytomegalovirus rather than HIV triggers the outgrowth of effector CD8+CD45RA+CD27- T cells in HIV-1-infected children.
OBJECTIVE
To analyse the effect of viral coinfections on immune reconstitution in HIV-1-infected children (< 18 years) taking highly active antiretroviral therapy (HAART).


METHODS
Absolute lymphocyte numbers of various subsets of CD8 T cells were measured.


RESULTS
Prior cytomegalovirus (CMV) infection correlated with an increased number of CD8 effector T cells (i.e., CD45RA+CD27-) at baseline (CMV-seropositive versus CMV-seronegative patients; P = 0.009), as well as an increased state of T cell activation as defined by HLA-DR and CD38 expression. The expansion of effector CD8 T cells persisted over time, independent of the HIV response to HAART. Numbers of CD8 effector T cells were significantly higher in patients with CMV replication as reflected by persistent urinary CMV shedding and periodic CMV DNAaemia (P = 0.02). These patients also showed an increase in CMV-specific antibodies compared with those without CMV shedding (P = 0.007). The number of CMV-specific interferon-gamma (IFN-gamma)-producing CD8 T cells was lower in children who persistently shed CMV compared with those who did not (P = 0.02). In contrast, CMV-specific CD4 T cell responses were detected at similar levels in both groups.


CONCLUSIONS
In HIV-1-infected children, CMV infection correlated with the outgrowth of CD8+CD45RA+CD27- effector T cells. Activation of the immune system by persistent CMV secretion resulted in increasing CMV-specific IgG and higher numbers of CD8 effector T cells. Despite these increases, the CMV-specific IFN-gamma-producing CD8 T cell response was diminished, which could explain the inability to suppress CMV completely in 41% of HIV-1-infected children.
Bekker
Vincent
V
Emma Children's Hospital, Sanquin Research and Landsteiner Laboratory, Academic Medical Center fInternational Antiviral Therapy Evaluation Center, Amsterdam, The Netherlands.
Bronke
Corine
C
Scherpbier
Henriëtte J
HJ
Weel
Jan F
JF
Jurriaans
Suzanne
S
Wertheim-van Dillen
Pauline M E
PM
van Leth
Frank
F
Lange
Joep M A
JM
Tesselaar
Kiki
K
van Baarle
Debbie
D
Kuijpers
Taco W
TW
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D012367:RNA, Viral / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D012367:RNA, Viral; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens