Jacques Theze

..Our studies have opened the door to cytokine-based immunotherapy and to the development of new drug- and vaccine-based strategies...

..Our new findings should help to guide antiretroviral therapy and vaccination strategies...

..A mutant form of p1-30 (Asp20-->Lys), which is likely unable to induce vascular leak syndrome, remains capable of generating LAK cells, like the original p1-30 peptide. Altogether, our data suggest that p1-30 has therapeutic potential...

..We discuss major controversies in the field and the relevance of the study of HIV controllers for the development of novel therapeutic strategies and vaccines...

....

..IL-7 responsiveness is only partly restored by HAART...

..This may be due to abnormal activation of the immune system in HIV-infected patients and may contribute to the reduced CD4 count and the altered function of the CD8 compartment...

..Thus, HIV infection perturbs IL-7 responses at both receptor binding and signaling steps, which likely compromises the regenerative capacity of the CD4(+) T-cell pool and may contribute to CD4(+) T-cell depletion...

..We investigated CCR7 expression and chemotactic function in patient T cells, to gain further insights into mechanisms of T-cell dysfunction in HIV infection...

..IL-7, based therapy, combined with efficient antiretroviral treatment, may be beneficial to HIV-infected patients by promoting thymic output, sustaining naive T cell counts and increasing memory T cell activation...

..In conclusion, HIV controllers maintained a population of highly efficient Th1 effectors directed against Gag in spite of a persistently low antigenemia, while patients treated in the long term showed a loss of CD4 effector functions...

..A positive correlation was found in a cohort of 18 patients between pre-HAART IL-7 plasma levels and CD4 cell increases after 20 +/- 7.8 months of HAART...

..We set to investigate the nature of IL-7-dependent signaling defects in patients with progressive HIV-1 infection...

..Thus, HIV controllers harbor a pool of memory CD4+ T cells with the intrinsic ability to recognize minimal amounts of Gag antigen, which may explain how they maintain an active antiviral response in the face of very low viremia...

..Thus, early events leading to IL-7 signal transduction involve its receptor compartmentalization into membrane nanodomains and cytoskeleton recruitment...

..These findings suggest the induction of an efficient, nondetrimental type of immune activation in patients who spontaneously control HIV...

..Such a program may prevent excessive human NK cell activation by effectors of innate immunity and regulate the transition between the innate and adaptive stages of immune responses...

..IL-2Rbeta/IL-2Rbeta could represent either a decoy receptor or a new form of IL-2R involved in signaling when gammac expression is low...

..But in CD8 lymphocytes, IL-2 down-modulates p27(kip1). These results indicate that, aside from IL-2R expression and function, IL-2 responsiveness is also controlled by lineage-specific mechanisms...

..By contrast, IL-2 induces the rapid disappearance of IL-2Rα and γ(c) chains when the gene transcription is downregulated, shutting down IL-2-responses as demonstrated by the absence of STAT5 phosphorylation and BCL2 expression...

..Radial microtubules disappear 15 min later, while transversal microtubules, independent of phospho-STAT5 transport, begin to bud from the microtubule organization center...

..Together our results indicate that both NK and PMN cells play a central role in the late events of IL-2-induced VLS...

..Increased TSLP responses point to a compensatory homeostatic mechanism that may mitigate defects in γc cytokine responses...

..This supports the hypothesis that aside from stimulating CD4 T cells IL-2 may also indirectly affect lymphocyte production through the stimulation of lymphopoietic cytokines...

....

....

..These results suggest that FLIP, in conjunction with other IL-2-regulated genes previously characterized in our laboratory, is involved in controlling lymphoadenopathy in IL-2(-/-) mice...