Kinetics of the T-cell receptor CD4 and CD8 V beta repertoire in HIV-1 vertically infected infants early treated with HAART.
OBJECTIVE
To determine the kinetics and the relationship between the T-cell receptor V beta (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up.


METHODS
Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out.


METHODS
Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy.


RESULTS
HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response.


CONCLUSIONS
These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.
Romiti
M L
ML
Division of Immunology and Infectious Diseases, Children's Hospital Bambino Gesu, Rome, Italy.
Cancrini
C
C
Castelli-Gattinara
G
G
Di Cesare
S
S
Ciaffi
P
P
Bernardi
S
S
De Gasperi
M R
MR
Halapi
E
E
Rossi
P
P
D023241:Antiretroviral Therapy, Highly Active; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D007700:Kinetics; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016896:Treatment Outcome; D019562:Viral Load
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta