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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Porcellini
Simona
S
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano, Milano, Italy.
Vallanti
Giuliana
G
Nozza
Silvia
S
Poli
Guido
G
Lazzarin
Adriano
A
Tambussi
Giuseppe
G
Siccardi
Antonio G
AG
Grassi
Fabio
F
D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D038041:Lymphopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D014779:Virus Replication
D019380:Anti-HIV Agents; D007376:Interleukin-2