AEGiS-15IAC: In vitro effects of IL-7 on post-thymic maturation pathways.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

In vitro effects of IL-7 on post-thymic maturation pathways.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1045)

Biasin M, Schenal M, Lissoni F, Trabattoni D, Gori A, Clerici M
Department Immunol, University Milano, Milano, Italy

BACKGROUND: IL-7 is required for thymopoiesis and enhances the peripheral expansion of mature T cells after T-cell depletion in animal models; this cytokine might therefore have a role as an immunomodulant in the therapy of HIV infection. We analysed the in vitro effect of IL-7 in PBMC of HIV-infected patients and uninfected controls (HC).

METHODS: PBMC of HIV patients and of HC were incubated in the presence/absence of hrIL-7 (10 ug/ml,) or hrIL-2 (100 UI/ml)(control cytokine). The following T lymphocyte subpopulations were evaluated by FACS after 24 or 48 hours: CD4 naïve (CD4+/45RA+/CCR7+/CD62Lh); CD4 central memory (CM) (CD4+/45RA-/CCR7+/CD62Lh); CD4 effector memory (EM) (CD4+/45RA-/CCR7-/CD62Ll); CD8 naïve (CD8+/45RA+/CCR7+/CD62Lh); CD8 CM (CD8+/45RA-/CCR7+/CD62Lh); CD8 EM (CD4+/45RA-/CCR7-/CD62Ll); CD8 terminally differentiated (TD) (CD8+/45RA+/CCR7-).

RESULTS: In HIV patients IL-7 did not modify the number of CD8 naïve, CD8 EM, or CD8 TD lymphocytes but it sharply increased the low perforin-exp ressing CD8 CM T cells. In contrast, in HC, IL-7 was associated with a reduction of CD8 naïve and CD8 CM cells and a sharp increase in the perforin-enriched CD8 TD lymphocytes. IL-7 did not modify CD4 naïve cells, augmented CD4 EM and diminished CD4 CM in HIV patients, whereas it decreased CD4 naïve and CD4 EM cells and increased CD4 CM (high IL-2 producing cells) in HC. Incubation with IL-2 did not result in significant changes in lymphocyte subpopulations.

CONCLUSIONS: The in vitro effects of IL-7 on post-thymic T lymphocyte maturation are different when PBMC of HIV-infected or -uninfected individuals are analysed. Thus, in HIV patients IL-7 results in the expansion of low IL-2-producing CD4 and of low-perforin-expressing CD8 T lymphocytes. Additionally, whereas in HC IL-7 seems to stimulate the differentiation of naïve lymphocytes, in HIV patients this cytokine induces shifts in the subpopulations of memory cells independently of a maturation of naïve lymphocytes.

Keywords: AEGIS, Thymus Gland, Interleukin-7, CD8-Positive T-Lymphocytes, Antigens, CD8, CD4-Positive T-Lymphocytes, Antigens, CD4, HIV, HIV Infections, Acquired Immunodeficiency Syndrome, Interleukin-2, Cytokines, Lymphocyte Subsets, HIV Seropositivity, Lymphocytes, Flow Cytometry, HIV Core Protein p24, In Vitro, Humans, immunology

040711
MoOrA1045