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Abstract
ADJUVANT SCIL2 INCREASES THYMIC PRODUCTION IN PATIENTS WITH ADVANCED HIV INFECTION UNDER ANTIRETROVIRAL THERAPY
KORTHALS ALTES H, SAINT-MEZARD P, TUBIANA R, DE BOER R, KATLAMA C, AUTRAN B, CARCELAIN G
Interleukin-2 (IL-2) increases CD4+ T cell numbers by enhancing mature T cell proliferation but its effect on naive T cell homeostasis and thymic function is unknown. Here we investigate whether IL-2 enhances thymic production, generally associated with a clinically beneficial recovery of repertoire diversity, in patients with advanced HIV infection and failing immune reconstitution despite highly active antiretroviral therapy (HAART). 12 patients with CD4 counts below 200/mm3 but controlled viremia under HAART were treated with additional adjuvant sub-cutaneous IL-2. Naive T cells as well as signal joint T-cell receptor excision circles (sjTRECs) in CD4 cells were counted in each patient over 80 weeks. A mathematical model was formulated describing the turnover of naive CD4 cells and sjTRECs. Parameters relating to thymic production (sigma), netto death rate (deltaN) and average sjTREC content of naive cells (c) were estimated through a non-linear fitting procedure. Our mathematical analysis suggests that the increase in naive T cells resulting from IL-2 administration is due to increased thymic production. In the six patients in which the sjTRECs do not increase under IL-2, a decreased average sjTREC content of recent thymic emigrants (c) is found. This suggests that in these cases IL-2 increases post-rearrangement expansion of thymocytes, leading to an enhanced production of naive cells with low sjTREC content.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
104
Suggested Citation
"KORTHALSALTESH, et al.
ADJUVANT SCIL2 INCREASES THYMIC PRODUCTION IN PATIENTS WITH ADVANCED HIV INFECTION UNDER ANTIRETROVIRAL THERAPY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
104"
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