Showing papers by "Marcello Pinti published in 2006"

Thymic output and functionality of the IL‐7/IL‐7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life

Abstract: During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T-cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T-cell receptor rearrangement excision circles (TREC). A new method based upon real-time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six-color cytofluorimetric analysis revealed that centenarians had an extremely low number of naive T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7 receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naive T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long-living lymphocytes that have not yet encountered their antigen. IL-7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.

Immunophenotype of HIV+ patients during CD4 cell-monitored treatment interruption: role of the IL-7/IL-7 receptor system.

Abstract: OBJECTIVE: To investigate immunological changes during CD4-guided therapy interruption in HIV(+) patients who suspended HAART. PATIENTS: Seventeen patients aged > 18 years, who had received HAART for at least 12 months, and had a pre-interruption CD4+ cell count > 500 cells/microl, interrupted treatment. Median nadir CD4(+) cell count was 288 cells/microl. HIV plasma viral load at discontinuation was 50 copies/ml. Criteria for restarting treatment were: a CD4(+) T-lymphocyte count < 350 cells/microl on two separate occasions, a clinical manifestation of AIDS, and the patient's desire to resume HAART. Eleven patients were still off therapy after 12 months (group A); according to the first criterion, six patients restarted therapy within 12 months (group B). METHODS: Haematological, viro-immunological, cytofluorimetic and molecular assays were performed at baseline and every 2 months following standard methods. Statistical analysis was performed under Stata 7.0. RESULTS: In the first 2 months of treatment interruption, a significant increase in viral load and CD8(+) lymphocyte activation occurred. Then such parameters decreased and remained stable. In all patients, a decrease in CD4(+) lymphocytes took place as well, that affected in a similar manner naive, central memory, effector memory and terminally differentiated cells. Group B always presented lower amounts of CD4(+) effector memory lymphocytes. The expression of CD127 was always higher in group A. CONCLUSIONS: The loss of CD4(+) lymphocytes upon viral rebound is equal among naive and memory subsets. Patients with higher expression of CD127, who are likely to exert a better capacity to utilize endogenous interleukin-7 by T cells, could remain off therapy for longer periods.

Polymorphisms of fas gene: relationship with Alzheimer's disease and cognitive decline.

Abstract: The Fas antigen (CD95) is a cell surface receptor that mediates cell apoptosis signalling. Recent investigations have shown that Fas-regulated apoptosis was linked to neurodegenerative lesions in the

Quantitation of CD95 and CD95L mRNA expression in chronic and acute HIV-1 infection by competitive RT-PCR.

Abstract: Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by increased immune cell apoptosis. Apoptosis can be triggered by signals that arise from within the cell, or by signals that are elicited by binding of extracellular "death ligands" to their "death receptors," most of which belong to the tumor necrosis factor (TNF)-receptor family, such as CD95 (Fas/Apo-1). In immune cells the oligomerization of CD95, induced by its ligand CD95L, and the recruitment of different intracytoplasmic molecules that in turn activate FLICE/caspase 8 are crucial. To study the role of CD95/CD95L interactions during HIV-1 infection, we developed an original method based upon quantitative-competitive (QC) RT-PCR that allowed us to quantify the amounts of mRNA coding for the total (tCD95) and membrane (mCD95) forms of CD95. We first studied the expression of different forms of CD95 mRNA in a classical model of chronic HIV infection using two infected cell lines of different origin--lymphocytic (ACH-2) or monocytic (U1). We have shown that infected cells of monocytic origin preferentially produce the "protective" (soluble) form of CD95, and no detectable CD95L mRNA, while lymphoid cells produce more mRNA for the membrane form of CD95 (which triggers apoptosis) along with low but detectable amounts of CD95L mRNA. One can hypothesize that a complex balance exists between pro-apoptotic events, perhaps triggered by the host to limit viral production, and anti-apoptotic events likely triggered by the virus to increase its production and survival. In cells of monocytic origin, which act as a reservoir for the virus, the anti-apoptotic molecules are favored; in cells of lymphocytic origin, molecules with an apoptotic meaning are prevalent.