[14] INTERLEUKIN-7 STIMULATES T-CELL RENEWAL WITHOUT INCREASING VIRAL REPLICATION IN SIV-INFECTED MACAQUES

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] INTERLEUKIN-7 STIMULATES T-CELL RENEWAL WITHOUT INCREASING VIRAL REPLICATION IN SIV-INFECTED MACAQUES

[AUTHOR(S):] MT Nugeyre¹, V Monceaux², S Beq¹, MC Cumont², R Ho Tsong Fang², L Chêne¹, M Morre³, F Barré-Sinoussi¹, B Hurtrel², N Israël¹
¹Unité de Biologie des Rétrovirus Institut Pasteur, Paris, France; ²Unité de Recherche et d’Expertise Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France; and ³Cytheris, Vanves, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 14
Antiviral Therapy 2003; 8(Suppl. 1):S188

[ABSTRACT:] Purpose of study: The main failure of antiretroviral therapy is the lack of restoration of HIV specific CD4 T cells. Interleukin 7 (IL-7) which has been shown to be a crucial cytokine for thymopoiesis has been envisaged as an additive therapeutic strategy. However in vitro studies suggest that IL-7 might sustain HIV replication in thymocytes and T lymphocytes. Therefore, in the present study, we evaluate the effect of IL-7 on both T cell renewal and viral load in SIVmac-infected young macaques in the absence of antiretroviral therapy. This evaluation was carried out during the asymptomatic phase in view of a potential treatment in HIV patients.

Experimental procedure: Healthy or infected animals were treated with recombinant human IL-7 (80 µg/kg during 21 days). The parameters followed (up to a month after interruption of IL-7 treatment) were: the weight, the blood formula, the absolute numbers of B, CD4, CD8 T lymphocytes. The effect of IL-7 on thymic function was evaluated by the number of naïve CD4 and CD8 T cells (CD45RA CD62L) together with the number of TREC. The rate of activated cells was evaluated as the number of CD4 and CD8 expressing the HLADR activation marker. The rate of peripheral expansion was determined as the rate of CD4 and CD8 expressing the nuclear marker Ki67. The viral load was determined in the serum (real time quantitative RT-PCR) and in lymph nodes and thymus (in situ hybridization of the viral genome).

Results and conclusions: We show here that IL-7 induces both a central renewal and a peripheral expansion of T lymphocytes associated with cell activation. No increase in the viral load was shown in blood or lymph nodes. Furthermore no alarming side effect was observed. These data strengthen the rationale for the use of IL-7 as an efficient immunotherapy in AIDS.

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