Preserved immune system in long-term asymptomatic vertically HIV-1 infected children.
The objective of this study was to study immune system status in long-term asymptomatic (LTA) HIV-1-infected children. A cross-sectional study was used, involving HIV-1-infected children over 7 years of age who were rated into two groups according to their clinical and immunological classification: (a) LTA: 7 asymptomatic HIV-1-infected children in A1; (b) Rapid progressor (RP): 14 age-matched C3 HIV-1-infected children. The control group consisted of 17 age-matched uninfected children. The characterization of CD4+ T-cell subsets was determined by three-colour flow cytometry. The proliferative response and cytokine production by activated peripheral blood T-cells were also measured. IL-7 levels were measured in serum. Thymic production of T-cells was quantified by TCR rearrangement excision circles (TRECs). The LTA children showed similar proliferative responses to PHA, PWM and anti-CD3+ anti-CD28, but lower responses to tetanus toxoid and streptokinase, in comparison with the controls but always higher responses in comparison with the RP group. The production of TNF-alpha and IFN-gamma was similar in the LTA and control groups, and both were higher than the levels in the RP group. The LTA group showed a lower percentage of memory CD4+ T-cells (CD4+ CD45RO+, CD4+ CD45RA-CD62L+) than the control and RP groups. The LTA group also showed lower percentages of CD4+ CD7- cells than the controls. As for naïve CD4+ T-cells (CD4+ CD45RA+ CD62L+), CD4+ CD45RA+ and CD4+ CD62L+ cells, the LTA group showed higher values than the control and RP groups. The LTA group showed higher percentages of CD4+ HLA-DR+ CD38+ than the controls, but lower values than the RP group. In contrast, the LTA group had percentages of CD4+ HLA-DR-CD38+ T-cells higher than both the control and RP groups, whereas CD4+ CD38+ levels were only higher in the LTA group in comparison with the controls. CD4+ HLA-DR+ CD38- and CD4+ HLA-DR+ cell numbers were lower in the LTA group in comparison with the RP group. We found almost normal values of TRECs and IL-7 in the LTA group, but lower values in the RP group. Moreover, we found an inverse relation between TREC levels and IL-7 in plasma from HIV-infected children. Asymptomatic HIV-1 infected children have a well preserved immune system similar to that of control uninfected children in spite of HIV-infection for more than 7 years. Moreover, our results identified new markers of HIV disease, such as TRECs and IL-7, that could be used to monitor disease.
Resino
S
S
Laboratory of Immno-Molecular Biology, General University Hospital 'Gregorio Marañón', Madrid, Spain.
Correa
R
R
Bellón
J M
JM
Muñoz-Fernández
M A
MA
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D015851:Interleukin-7 / Q000097:blood; D018655:Lymphocyte Count; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D017735:Virus Latency
D015851:Interleukin-7