512-M. Limited Thymic Contribution to Initial CD4 T-Cell Restoration during Supplementation of HAART with IL-2 and/or Remune

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Session 70 Poster Session
Thymic Function and Immune Reconstitution
Session Time: 4:30-6:30 pm
Room 4E-F

512-M.

Limited Thymic Contribution to Initial CD4 T-Cell Restoration during Supplementation of HAART with IL-2 and/or Remune
J. Pido-Lopez*, C. Burton, G. Hardy, A. Pires, R. Aspinall, B. Gazzard, F. Gotch, and N. Imami
Imperial Coll. of Sci., Technology and Med., London, UK

Background: Our objective was to determine the effect of treatment with HAART alone or in conjunction with interleukin-2 (IL-2) and/or immunization with inactivated gp120-depleted immunogen (Remune) on the thymic function of HIV-1-infected individuals.
Methods: The T-cell receptor excision circles (TRECs) assay was utilised to identify and quantify the number of recent thymic emigrant T cells in the peripheral blood of HIV-1-infected individuals receiving HAART alone (group A) n=7, HAART+IL-2 (group B) n=6, HAART+IL-2+Remune (group C) n=7, or HAART+Remune (group D) n=6 as a measure of their thymic output during 70 weeks of therapy. Viral loads, CD4 and CD8 T-cell numbers were also measured.
Results: TREC levels were observed to decline progressively in the first 35 weeks of therapy in patients receiving HAART+IL-2 and/or Remune and later showed signs of recovery from week 50 onwards. Patients on HAART alone failed to show notable changes in TRECs throughout the study. Patients’ viral loads remained generally constant throughout while CD4 T-cell counts increased for the first 15 weeks of therapy in group B and C patients and slowly declined thereafter. Group A and D patients’ CD4 counts remained uniform throughout. CD8 T-cell numbers remained generally constant throughout for patients in group A, C, and D. Group B patients showed increases in CD8 cells in the first 10 weeks of therapy and a steep rise from week 50 onwards.
Conclusions: Despite early increases in CD4 and total T-cell numbers during the first 20 weeks of therapy in patient groups B and C, TREC levels were observed to decline during this time. These results indicate little thymic contribution to CD4 restoration and suggest proliferation and/or redistribution as the mechanism responsible for CD4 rises as well as the TREC decline, as a result of dilution. Increases in CD4 and total T-cell numbers accompanied by rises in TRECs initiating at week 50 suggests a late contribution by the thymus to cell restoration. Initial decline in TRECs in patients receiving IL-2 and/or Remune with HAART indicate that thymic independent mechanisms of proliferation and/or redistribution are the means by which such agents aid initial T-cell restoration in HIV-1-infected patients.