Early effects of antiretroviral combination therapy on activation, apoptosis and regeneration of T cells in HIV-1-infected children and adolescents.
OBJECTIVE
To assess the relationship between apoptosis, activation and regeneration of T cells, and viral replication in paediatric patients with HIV-1 infection during antiretroviral therapy (ART).


METHODS
In 15 HIV-1-positive children and adolescents sequential blood samples were obtained during 16 episodes of ART using combinations of nucleosidic HIV-1 reverse transcriptase (RT)-inhibitors and HIV-1 protease inhibitors or non-nucleosidic RT-inhibitors.


METHODS
We assessed sensitivity of freshly isolated peripheral blood T cells towards spontaneous, anti-CD95- and anti-CD3-induced apoptosis and activation before and after 6-8 weeks of ART. Expression of CD95, CD45RA, CD45RO and CD62L on CD4 and CD8 T cells and of CD34 on mononuclear cells was studied by multiparameter flow cytometry before and after 10-12 weeks of ART.


RESULTS
ART caused a significant increase in absolute lymphocyte and CD4 T cell counts (P < 0.03 and P < 0.02, respectively) and a decrease in both anti-CD95- and anti-CD3-induced apoptosis of CD4 and CD8 T cells to near normal levels even in patients without complete suppression of viral replication. A significant reduction in the percentage of CD95 (but not of CD95high) CD4 T cells was observed (P < 0.005). Resting/naive cells contributed significantly (P < 0.03) to the rise in CD4 T cells especially in infants and young children.


CONCLUSIONS
Different mechanisms may contribute to early T cell reconstitution in HIV-1-infected children and adolescents during ART: decreased activation-induced apoptosis leading to increased survival of circulating primed/memory T cells; decreased activation-induced naive-to-memory shift increasing the frequency of circulating resting/naive T cells; increased input of haematopoietic progenitor cells from the bone marrow into the thymus and decreased intrathymic T cell death leading to an increased thymic output of naive T cells.
Böhler
T
T
Division of Molecular Oncology, German Cancer Research Center, Heidelberg.
Walcher
J
J
Hölzl-Wenig
G
G
Geiss
M
M
Buchholz
B
B
Linde
R
R
Debatin
K M
KM
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D019380:Anti-HIV Agents; D012367:RNA, Viral