Improved thymopoietic potential in aviremic HIV infected individuals treated with HAART by intermittent IL-2 administration

• Published in: AIDS (London) Vol. 17; no. 11; pp. 1621 - 1630
• Main Authors: Porcellini, Simona, Vallanti, Giuliana, Nozza, Silvia, Poli, Guido, Lazzarin, Adriano, Tambussi, Giuseppe, Siccardi, Antonio G, Grassi, Fabio
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 25.07.2003
• Subjects: Adult; Animals; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Cells, Cultured; Female; Flow Cytometry; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - physiology; Human viral diseases; Humans; Infectious diseases; Interleukin-2 - therapeutic use; Lymphopoiesis - drug effects; Medical sciences; Mice; Mice, Inbred C57BL; Middle Aged; Pharmacology. Drug treatments; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Replication; HIV-1; foetal thymic organ cultures; interleukin-2; thymus; HIV-1 virus; Interleukin 2; Immunological investigation; Intermittent; T-Lymphocyte; Antiviral; Immunopathology; Thymus gland; Retroviridae; Immune reconstitution; AIDS; Immune deficiency; Lentivirus; Infection; Virus; T cell development; Chemotherapy; Treatment; T cell receptor excision circle; Viral disease; Human immunodeficiency virus; T cell receptor excision circles
• DOI: 10.1097/00002030-200307250-00006
• ISSN: 0269-9370

In HIV-positive individuals administration of intermittent interleukin (IL)-2 in addition to highly active antiretroviral therapy (HAART) induces expansion of the peripheral T cell pool with dilution of signal joint T cell receptor excision circles (sjTREC) that cannot be used to measure thymic output. We analysed whether in vitro thymopoiesis could be used to predict in vivo thymic output in IL-2 treated subjects. We correlated the relative variation of peripheral CD4 T cells over 12 months in HIV-positive subjects on HAART or HAART + IL-2 with the mean levels of both sjTREC and T cells developed in chimeric murine foetal thymic organ cultures (FTOC) reconstituted with circulating progenitors. In contrast with HAART treated individuals in which these values were directly correlated, in subjects receiving HAART + IL-2 the increase of CD4 T cells in vivo was correlated to neither sjTREC number nor to reconstitution of FTOC, probably reflecting a main effect of IL-2 in the expansion of the peripheral T cell pool. Nevertheless, addition of IL-2 to HAART determined a significant increase of in vitro thymopoietic potential in individuals with undetectable viraemia. The increased T cell development in vitro after addition of IL-2 to HAART suggests that intermittent IL-2 administration may exert a positive influence on lymphopoiesis. In two subjects with positive viraemia treated with IL-2 we observed reduced in vitro development of T cell precursors suggesting that the positive influence of IL-2 on thymopoiesis could be secondary to the control of viral replication by HAART. These observations provide novel evidence in support of the potential beneficial use of IL-2 in HAART treated individuals.