350   Increase of Thymic Production (TRECs) After Adjuvant scIL2 Therapy in Advanced HIV Patients Treated by HAART.

P. Saint-Mezard¹, R. Tubiana¹, M. De Sa¹, C. Rabian², P. Debre¹, C. Katlama¹, B. Autran¹, and G. Carcelain*¹.
¹Pitié-Salpétrière Hosp. and²Saint-Louis Hosp., Paris, France.

Background:IL2 is known to increase CD4 T cell numbers by enhancing mature T cell proliferation. We now investigated whether IL2 also enhances thymic production by measuring T-cell receptor excisional circles (TRECs) in CD4⁺T cells in advanced patients with a severe depletion of naive CD4 T cells and failure in immune reconstitution despite efficient HAART.

Methods:14 patients with CD4 <200/mm³and VL <1000 copies/ml, treated with HAART, received adjuvant scIL2 4.5 MIU bid in 4 cycles every 6 weeks (W), half from day (D) 0 to W50—52 and half after a delayed period of 24W. Eight age-matched healthy individuals were used as controls. CD4 subsets were evaluated on fresh cells by flow cytometry using anti-CD45RO/RA and anti-CD62L mAbs. The proportion of recent thymic emigrants (RTE) had been quantified by a real-time PCR assay (Taqman) for SjTRECs both in PBMCs and in purified CD4⁺T cells.

Results:The number of TRECs of HIV⁺patients measured at D0 expressed per 10⁶PBMC decreased with the age with a slope of -0.02 log/year. This decrease was similar to the one observed in the age-matched controls. IL2 therapy induced a significant increase in the percentage and the number of naive CD4⁺T cells (CD4⁺CD45RA⁺CD62L⁺) and of memory CD4⁺T cells (CD45RO⁺). In 11/14 cases the naive CD4 T cell number increase was paralleled by an increase of the number of TRECs in the CD4 T cells subset.

Conclusions:An increase of TRECs is associated with IL2 therapy in advanced patients. These data demonstrate that the effects of IL2 therapy do not reflect only peripheral proliferation of CD4⁺memory T cells but also reflect participation of thymic production.