Biomedical subjects

L Cosmi

Publications and source records attributed to L Cosmi.

24 records · Page 2Linked to original sources

PubMed1998

Enhanced HIV expression during Th2-oriented responses explained by the opposite regulatory effect of IL-4 and IFN-gamma of fusin/CXCR4.

The human alpha-chemokine receptor fusin/CXCR4 is an important cofactor for entry of T lymphocyte-tropic HIV-1 strains. We investigated the possible regulatory role of T cell cytokine patterns on CXCR4 as well as HIV expression by using in vitro models of both secondary and primary immune responses. Antigen-specific memory CD4+ T cells infected with a T-tropic HIV-1 strain showed significantly higher CXCR4 and HIV-1 expression in Th0/2-oriented responses in comparison with Th1-oriented responses. Similarly, in naive CD4+ T cells activated in the presence of IL-4 or IL-12 and infected with the same T-tropic strain, IL-4 up-regulated whereas IL-12 down-regulated both CXCR4 and HIV-1 expression. The down-regulatory effect of IL-12 on CXCR4 expression was found to be dependent on its capacity to induce IFN-gamma production. These observations can account for the higher risk of progression in HIV-1-infected individuals undergoing Th0/2-oriented immune responses.

Cells, Cultured↗

PubMed1998

Molecules associated with human Th1 or Th2 cells.

In the last few years, some surface molecules which preferentially associate with human Th1 or Th2 cells have been described. Th1-related molecules include CD26, membrane IFN-gamma, LAG-3, CCR5 and CXCR3, whereas CD62L, CD30, CCR3, CCR4, CCR8, and in a certain way even CXCR4, preferentially associate with human Th2 cells during certain phases of their differentiation/activation process. Although none of these molecules can be considered as a truly selective marker of human Th1 or Th2 cells, their combined detection may help to characterize the pathway of the specific immune response both in vitro and in vivo. Moreover, the understanding of mechanisms responsible for these associations may provide new insights into the functional programs of the specific effector cells, as well as on their regulation.

Animals↗

PubMed1997

Functional characterization and modulation of cytokine production by CD8+ T cells from human immunodeficiency virus-infected individuals.

CD8+ T-cell clones were generated from peripheral blood mononuclear cells (PBMC) of three human immunodeficiency virus (HIV)-seronegative individuals and six HIV-seropositive individuals and assessed for their cytokine secretion profile, cytolytic potential, and chemokine production. While the great majority of CD8+ T-cell clones generated from HIV-seronegative individuals produced interferon (IFN)-gamma, but not interleukin-4 (IL-4), that is a type 1 cytotoxic (Tc1) profile, high numbers of CD8+ T-cell clones generated from HIV-seropositive individuals produced IL-4 in addition to IFN-gamma or IL-4 alone, thus showing a type 0 cytotoxic (Tc0)- or a type 2 cytotoxic (Tc2) profile, respectively. Tc0/Tc2 cells displayed lower cytolytic activity than Tc1 cells, including a reduced ability to lyse autologous targets pulsed with HIV or HIV peptides. By contrast, the production of chemokines RANTES and macrophage inflammatory protein-1alpha was comparable in Tc1, Tc0, and Tc2 clones irrespective of whether they were derived from HIV-seronegative or HIV-seropositive individuals. When CD8+ T-cell clones were generated from PBMC cultures of HIV-seronegative individuals conditioned with IL-4 plus an anti-IL-12 antibody (Ab), a shift towards the Tc0/Tc2-like profile was observed. Conversely, the addition to PBMC cultures of IL-12 plus an anti-IL-4 Ab shifted the differentiation of CD8+ T cells from HIV-infected individuals towards the Tc1-like profile, whereas IL-12 or anti-IL-4 Ab alone had a lower Tc1-promoting effect. Irradiated PBMC from HIV-infected individuals, used as feeder cells, shifted the differentiation of CD8+ T cells from a healthy HIV-seronegative individual towards the Tc0/Tc2-like profile. On the other hand, a shift towards the Tcl-like profile was noted in CD8+ T-cell clones generated from the skin specimens of two HIV-seropositive patients with Kaposi's sarcoma, successfully treated with IFN-alpha, in comparison to CD8+ clones generated from the same skin areas before treatment. The IFN-alpha-induced Tc1 shift could be prevented by the incubation of skin-infiltrating CD8+ T cells with IL-4 before cloning. Taken together, these data indicate that both defective production of IL-12 and abnormal IL-4 production in bulk PBMC populations of HIV-infected individuals may contribute to the development of high numbers of CD8+ T-cell clones showing a Tc0/Tc2-like phenotype and reduced cytolytic potential against HIV itself. They also suggest that the cytokine profile of CD8+ T-cell clones can be modulated by cytokines (or anticytokine Ab) both in vitro and in vivo.

Antibodies, Monoclonal↗

PubMed1997

Opposite role for interleukin-4 and interferon-gamma on CD30 and lymphocyte activation gene-3 (LAG-3) expression by activated naive T cells.

Polarized human type 1 and type 2 T helper cells not only produce different sets of cytokines, but they also preferentially express certain activation markers, such as lymphocyte activation gene-3 (LAG-3) and CD30, respectively. In this study we have examined the LAG-3 and CD30 expression in relation to the lineage commitment of human naive CD4+ T cells, as assessed at the single-cell level of committed T cells. Purified CD45RA+ umbilical cord blood T lymphocytes were activated with phytohemagglutinin and interleukin (IL)-2 in the absence or presence of interleukin IL-4 or IL-12 and assessed for CD30 and LAG-3 expression, as well as for intracellular cytokine synthesis. Significant numbers of CD30+ cells were only found in CD4+ and CD8+ T lymphocytes of cultures primed with IL-4, which developed into cells able to produce IL-4 and IL-13 in addition to interferon (IFN)-gamma. By contrast, LAG-3 expression was strongly up-regulated in CD4+ and CD8+ T cells from cultures primed with IL-12, which developed into high numbers of IFN-gamma producers. The addition of a neutralizing anti-IFN-gamma antibody to IL-12-primed CD4+ T cell cultures virtually abolished the development of LAG-3-expressing CD4+ T cells. Taken together, these data suggest that CD30 expression is dependent on the presence of IL-4, whereas LAG-3 expression is dependent on the production of IFN-gamma during the lineage commitment of human naive T cells.

Antigens, CD↗

PubMedDate not supplied

Reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropyridine calcium channel antagonists.

PURPOSE: To evaluate reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropiridine calcium channel antagonists. PATIENTS AND METHODS: Fifteen patients, affected by essential arterial hypertension, were examined. They received once a day oral dihydropyridine calcium antagonists for 10 weeks: five patients received felodipine (5 mg), five amlodipine (10 mg) and five lercanidipine (10 mg). The levels of end products of lipid peroxidation, free radicals and hydroperoxides and total antioxidant capacity were determined in the plasma of all subjects before and during treatment. Values are expressed as mean +/- S.E. Systolic blood pressure decreased from 171 +/- 4 to 135 +/- 6 mmHg (p < 0.01) and diastolic blood pressure decreased from 99 +/- 5 to 82 +/- 3 mmHg (p < 0.01). Hydroperoxides and free radicals decreased from 321.3 +/- 8.96 to 247.9 +/- 8.69 units (p < 0.01) and the end products of lipid peroxidation decreased from 11.0 +/- 1.93 to 6.74 +/- 1.41 nmol/ml (p < 0.01). Total antioxidant capacity increased from 0.74 +/- 0.03 to 1.05 +/- 0.05 mmol/l (p < 0.01). RESULTS: Imbalance in the pro-oxidant-antioxidant equilibrium shifts in favour of antioxydant namely oxidative stress decreases. The calcium channel antagonists decrease peripheral arterial resistances and therefore decrease or abolish relative ischaemia, moreover decrease arterial pressure and therefore normalize parietal stress on endothelial cells. As a conseguence they act on two hypothesized mechanisms of oxidative stress in hypertension. CONCLUSIONS: Dihydropyridine calcium antagonists used in this trial seem useful in hypertension because they decrease oxidative stress, and normalize of pressure values.

Adult↗

PubMedDate not supplied

Th1 and th2 responses, HIV-1 coreceptors, and HIV-1 infection.

The Th1/Th2 model provides an interesting paradigm for understanding several pathophysiological processes and possibly for developing new immunotherapeutical strategies. In HIV-1 infection the interaction between the type of HIV-1 strain and the pathway of the ongoing T-cell effector response, despite its complexity, may represent one of the crucial mechanisms in determining the outcome of virus infection. While the possibility of an HIV-1-driven Th1 to Th2 switch of the immune response is still debated, evidence is accumulating to suggest that cytokines produced during an immune response can contribute to promote a selective pressure toward the evolution of HIV-1 viral strains with different tropism. This article summarizes the results of our recent studies in which the expression of CCR5 and CXCR4 HIV-1 co-receptors, as well as the activity of R5- or X4- tropic strains of HIV-1 in different in vitro models of Th1/Th2 polarization was analyzed.

Acquired Immunodeficiency Syndrome↗