AEGiS-13IAC: Relative contribution of naive and memory T cells to the restoration of cytokine production following HAART.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Relative contribution of naive and memory T cells to the restoration of cytokine production following HAART.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB487)

Ledru E, Patey O, Roue R, Gougeon M-L
E. Ledru, Pasteur Institute, 25 Rue du Dr Roux, 75015 Paris, France, Tel.: +33 1 45 68 89 14, Fax: +33 1 45 68 89 09, E-mail: eriledru@pasteur.fr

BACKGROUND: HAART is associated to a decrease in peripheral T cell apoptosis. As apoptosis regulates cytokine production, we assess the homeostasis of cytokine production in CD45RA and CD45RO T cells following HAART.

METHODS: 15 HIV+ patients naive of protease inhibitor (PI) were followed for 18 months. A cross sectional study involved 17 HIV- controls, HIV+ patients without PI (PI0, n = 16), treated with PI for less (PI1, n = 18) or more than 1 year (PI2, n = 12), and PI+ patients presenting with the lipodystrophy syndrome (LD, n = 15). Cytokine production and susceptibility to apoptosis of CD45RA and CD45RO subsets were assessed by flowcytometry following polyclonal stimulation.

RESULTS: Following 12 months of HAART, a 2.5 fold increase in the absolute number of TNFa+ T cells vs baseline values was observed. In contrast, the number of CD4 T cells producing IL-2 remained lower in PI+ patients vs controls. We revealed a defect in IL-2 production by the CD4+CD45RA+ subset, more pronounced in patients with the higher level of viral suppression. IL-2 production by CD4+CD45RO+ T cells, inversely correlated with the level of apoptosis, was restored vs controls in PI2, but not in LD, in whom the excess in apoptosis in IL2 producers was not controlled by the therapy. In CD8 T cells, the increased TNFa production was observed in both CD45RA and CD45RO subsets, and in the former this increase in was inversely related to the rate of apoptosis. LD patients showed a higher accumulation of CD8+CD45RO+TNFa+ cells than other PI patients.

CONCLUSIONS: Although IL-2 production by CD4+CD45RO+ cells is restored in some PI+ patients, a defect is still observed in the CD45RA subset. The control of T cell apoptosis could be involved in both the increased IL-2 production by CD4+CD45RO+ cells, and of TNFa by CD45RA T cells. Analysis of cytokine production by CD45RA+ cells could also allow a more accurate monitoring of true naive cells during HAART.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Antigens, CD45, CD4-Positive T-Lymphocytes, T-Lymphocytes, CD8-Positive T-Lymphocytes, Antigens, CD4, Interleukin-2, HIV Infections, Antigens, CD8, Apoptosis, Cross-Sectional Studies, Human, immunology
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WeOrB487