ABSTRACT
OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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.
Subject(s)
Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , HIV Infections/drug therapy , HIV Infections/immunology , Receptors, Antigen, T-Cell, alpha-beta/metabolism , CD3 Complex/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Flow Cytometry , HIV Infections/transmission , HIV Infections/virology , HIV-1/physiology , Humans , Infant , Infectious Disease Transmission, Vertical , Kinetics , Lymphocyte Activation , Treatment Outcome , Viral LoadABSTRACT
Assessment of the percentage and absolute number of T cells as well as of their main subpopulations is presently a routine procedure for the diagnosis and follow-up of a wide array of pediatric immunologic disorders. For several clinical applications (severe immunodeficiencies or leukaemias) the diagnostic usefulness of their enumeration does not require close comparison with age normal values, while in other circumstances such as follow-up of immunomodulating or immunosuppressive treatments or detection of minor immune defects, the expected changes of T cell subsets are more subtile and they are likely to be detected only by comparison with well-defined age normal values. In the present study CD3, CD4 and CD8 positive cells were enumerated in a group of 410 healthy children of age ranging from 30 days to 9 years. No significant changes in percentage or absolute number were observed during infancy and childhood. Furthermore the sum of CD4 and CD8 positive cells was close to the percentage of CD3 positive cells, suggesting a phenotype maturity of T cells from infancy.
