HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy.
Journal: 2004/October - Clinical and Experimental Immunology
ISSN: 0009-9104
Abstract:
The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11.8 +/- 0.4 (9.9; 15.4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0.05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4(+) T cell absolute counts (r = 0.558; P = 0.05) and percentages (r = 0.625; P = 0.030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4(+) and CD8(+) T cell subsets were increased significantly (P < 0.05). CD4(+) CD45RA(hi+) CD62L(+), CD4(+) CD45RA(+) and CD4(+) CD38(+) percentages, and the CD8(+) CD45RA(hi+) CD62L(+) counts reached similar values to the control group. Also, CD8(+) CD45RO(+) CD38(+) and CD8(+) CD45RO(+) percentages, and CD8(+) CD45RO(+) CD38(+) absolute counts (P < 0.05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0.001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG(1) and IgG(3) plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.
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Clin Exp Immunol 137(3): 570-577

HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy

Immunobiology Molecular Laboratory, Hospital General Universitario ‘Gregorio Marañón’, Madrid, spain
Immuno-Paediatric Department, Hospital General Universitario ‘Gregorio Marañón’, Madrid, spain
Unit of Paediatric Infectious Diseases, Hospital Universitario ‘Virgen del Rocío’, Sevilla, Spain
Correspondence: M Angeles Muñoz-Fernández, Laboratorio de Inmuno-biología, Hospital General Universitario ‘Gregorio Marañón, C/Doctor Esquerdo, 46.28007 Madrid, Spain. E-mail: se.mau.mbc@zonumM
Accepted 2004 Jun 28.

Abstract

The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11·8 ± 0·4 (9·9; 15·4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0·05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4 T cell absolute counts (r = 0·558; P = 0·05) and percentages (r = 0·625; P = 0·030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4 and CD8 T cell subsets were increased significantly (P < 0·05). CD4 CD45RA CD62L, CD4 CD45RA and CD4 CD38 percentages, and the CD8 CD45RA CD62L counts reached similar values to the control group. Also, CD8 CD45RO CD38 and CD8 CD45RO percentages, and CD8 CD45RO CD38 absolute counts (P < 0·05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-α and interferon (IFN)-γ production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0·001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG1 and IgG3 plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.

Keywords: cytokine, HAART, HIV-infected children, immunoglobulin, T cell subsets, TREC
Abstract

Acknowledgments

We wish to thank to Dolores García Alonso and Consuelo Muñoz for their excellent technical assistance. This study received financial support from the Fundación para la Investigación y la Prevención del SIDA en España, FIPSE (grant no. 36365/02, 12456/03), Comunidad de Madrid (grant no. 08·5/0034/2001), the Red Temática Cooperativa de investigación en SIDA (grant no. RIS G03/173) from FIS, the Red Temática Cooperativa de Investigación en Genética Clínica y Molecular (grant no. RIG C03/07) from FIS, Bristol-Myers, SA Squibb and Plan Nacional de Salud (grant no. SAF 2003–09209). Salvador Resino is supported by a grant from FIS (grant no. CM0300038).

Acknowledgments

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