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Biomedical subjects

E Maggi

Publications and source records attributed to E Maggi.

At least 109 records · Page 6Linked to original sources
PubMed1994

Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells.

Both interferon gamma (IFN-gamma) produced by T helper 1 (TH1) lymphocytes and interleukin-4 (IL-4) produced by TH2 lymphocytes were reduced in either bulk circulating mononuclear cells or mitogen-induced CD4+ T cell clones from the peripheral blood of individuals infected with human immunodeficiency virus (HIV). There was a preferential reduction in clones producing IL-4 and IL-5 in the advanced phases of infection. However, enhanced proportions of CD4+ T cell clones producing both TH1-type and TH2-type cytokines (TH0 clones) were generated from either skin-infiltrating T cells that had been activated in vivo or peripheral blood T cells stimulated by antigen in vitro when cells were isolated from HIV-infected individuals. All TH2 and most TH0 clones supported viral replication, although viral replication was not detected in any of the TH1 clones infected in vitro with HIV. These results suggest that HIV (i) does not induce a definite TH1 to TH2 switch, but can favor a shift to the TH0 phenotype in response to recall antigens, and (ii) preferentially replicates in CD4+ T cells producing TH2-type cytokines (TH2 and TH0).

Acquired Immunodeficiency Syndrome↗
PubMed1994

Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

Animals↗
PubMed1994

Activated and "memory" phenotype of circulating T lymphocytes in intrauterine life.

We examined the expression of T cell markers in the peripheral blood of five immunologically normal human fetuses at 18-20 weeks of gestational age. The distribution of T cells expressing CD1, CD3, CD4, CD8, CD56, and the alpha/beta and gamma/delta receptors for antigen was comparable to that of newborns and normal adults, except for the absence of gamma/delta cells expressing the delta TCS-1 epitope. The V beta repertoire, as evaluated by two-color flow cytometry using mAbs to specific V beta families, was also comparable to that of adult samples. A significant fraction (8.9 to 16.4%) of fetal CD3+ T cells expressed the alpha chain of IL-2R (CD25) in the absence of HLA-DR; this suggests that antigenic stimuli trigger, during intrauterine life, an unusual pathway of T cell activation. Consistent with this, 7 to 27% of fetal T cells were found to express the CD45R0 marker of "memory" cells.

Antigens, CD↗
PubMed1994

Th1 versus Th2 responses in AIDS.

During the past two years, a simple theory that seeks to explain what causes the progression of HIV-infected individuals to AIDS has been gaining support. The theory holds that HIV-infected people switch from a T-helper type 1 (Th1) to a T-helper type 2 (Th2) state as the disease progresses. However the experimental data do not support the concept that a Th1/Th2 switch occurs in the majority of HIV-infected subjects, although it is conceivable that HIV-infected individuals who mount sustained and chronic Th2-type responses, as a result of allergic disorders and helminthic infestations, may undergo more active HIV replication and therefore progress faster to full-blown disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Interleukin-1 favours the in vitro development of type 2 T helper (Th2) human T-cell clones.

The effects exerted by interleukin-1 (IL1) on the growth and differentiation of human Th1 and Th2 cells were examined. Neither IL1 nor the IL1 receptor antagonist (IL1ra) had detectable activity toward the antigen- or anti-CD3 antibody-induced proliferative response of already established type 1 T helper (Th1) or type 2 T helper (Th2) clones. Moreover, neither exogenous IL1 addiction to, nor neutralization of, endogenously produced IL1 in bulk cultures before cloning changed the Th1-like cytokine profile of PPD-specific T-cell lines. Likewise, IL1 addition in bulk culture before cloning did not significantly affect the Th2-like cytokine profile of Der.p.I-specific T-cell lines (Dermatophagoides pteronyssinus group I). However, Der.p.I-specific T-cell lines, derived in the presence of anti-IL1 Ab, IL1ra or the M-20 IL1 inhibitor, exhibited the reduced ability to produce IL4 and an increased ability to produce interferon gamma (IFN gamma). More importantly, Der.p.I-specific T-cell lines derived in the presence of IL1ra developed into Der.p.I-specific CD4+ T-cell clones showing a Th0/Th1-like, instead of a Th0/Th2-like, cytokine profile. These data suggest that IL1 is not required for the growth of already established human Th1 or Th2 CD4+ T-cell clones and has no regulatory effects on the in vitro development of Th1-like cells, but it plays a critical role in the development of Th2-like cells.

Animals↗
PubMed1994

Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis?

Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistance to Cu(++)-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation.

Arteriosclerosis↗
PubMed1994

Autoantibodies against oxidatively-modified LDL in uremic patients undergoing dialysis.

Target-specific oxidation processes in LDL generate molecular epitopes that are more atherogenic than the native forms and are able to elicit an immunological reaction leading to the formation of anti-oxLDL autoantibodies (oxLDL-Ab) that may participate in the overall process of atherogenesis. Thus, the detection of oxLDLAb, in addition to mirroring the occurrence of in vivo LDL oxidation, will give valuable information on the occurrence of this immune response. Plasma oxLDLAb (IgG and IgM) were measured in 72 control subjects (CS) and in 80 patients with chronic renal failure (CRF), undergoing repetitive hemodialysis (N = 56) or peritoneal dialysis (N = 24), with an ELISA method using native LDL, CuSO4-oxidized LDL (oxLDL) or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross reactivity of the antibodies detected with other oxidatively-modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed as antigens. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins. CRF patients had an antibody ratio significantly higher than CS as concerning anti-oxLDL IgG (1.39 +/- 0.36 vs. 1.05 +/- 0.3, P < 0.05) and IgM (2.15 +/- 0.75 vs. 1.43 +/- 0.43, P < 0.01), and anti-MDA-LDL IgG (3.05 +/- 0.74 vs. 2.04 +/- 0.42, P < 0.01) and IgM (5.55 +/- 1.79 vs. 2.9 +/- 0.85, P < 0.01). The anti-MDA-HSA antibody titer was also higher in CRF patients than in CS (2.49 +/- 0.5 vs. 1.46 +/- 0.39, P < 0.01 for IgG and 2.80 +/- 1.03 vs. 1.26 +/- 0.43, P < 0.01 for IgM).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗
PubMed1994

An alternative view of the Th1/Th2 switch hypothesis in HIV infection.

A theory that seeks to explain what induces the relentless progression of HIV-infected subjects to AIDS has received considerable attention. This theory holds that HIV infection results in a Th1/Th2 switch. However, analysis of constitutive cytokine mRNA expression in lymphoid tissues from HIV-infected individuals did not confirm an in vivo Th1/Th2 switch. Moreover, data available at the level of in vitro-stimulated peripheral blood mononuclear cells or cloned T cells do not provide clear evidence for a definite switch to the Th2 responses in any HIV-infected subject and in any phase of HIV infection. At most, currently available data on the profile of cytokines released in response to in vitro stimulation suggest a Th1-to-Th0 shift in a proportion of memory CD4+ T cells. On the other hand, experiments of in vitro infection with HIV of already established CD4+ T cell clones indicated that Th2 and Th0 cells support HIV replication better than Th1 cells, suggesting that early destruction of Th2 cells by direct or indirect HIV-mediated cell killing may occur. Finally, in some HIV-infected individuals with low CD4+ T cell counts, a prevalence of CD8+ T cells producing type 2 cytokines was found in both peripheral blood and skin. Thus, although the induction of a general Th2 state in HIV infection is not proven, enhanced production of type 2 cytokines may occur in a proportion of HIV-infected individuals and play some role in the pathogenesis of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO4. However, vitamin E efficiency was lower (9.6 +/- 4.2 versus 30.2 +/- 7.6 min/nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5 +/- 16.5 versus 58 +/- 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu(2+)-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Regression formula for estimation of fetal weight with use of abdominal circumference and femur length: a prospective study.

Ultrasonographic fetal measurements from 293 singleton pregnancies were obtained within 7 days of delivery. Biparietal diameter, abdominal circumference, femur length, and actual birth weight data of the first 93 fetuses in the study were used as variables to determine the best mathematical model for relating estimated fetal weight to biparietal diameter, abdominal circumference, and femur length. With the aid of a computer, three regression equations were derived. The best model was Log10 (weight) = 0.77125 + 0.13244 (AC) - 0.12996 (FL) - 1.73588 (AC x AC)/1000 + 3.09212 (FL x AC)/1000 + 2.18984 (FL/AC); (R2 = 0.987). The accuracy of this formula was then compared prospectively, first with the formulas published by Shepard and coworkers, Rose and McCallum, and Hadlock and colleagues in the entire sample of 200 patients, second in 46 large, 101 appropriate, and 53 small for gestational age fetuses, and then in 44 fetuses of pregnancy complicated by diabetes. The difference between actual and estimated birth weights generated by the study formula had no systematic error (Student's t-test, P > 0.05) in cumulative data, and in small or appropriate and large for gestational age fetuses. As this derived formula is very cumbersome to manipulate, tables have been prepared with computer assistance to read the estimated fetal weight directly.

Abdomen↗
PubMed1994

Molecular basis of cross-reactivity among allergen-specific human T cells: T-cell receptor V alpha gene usage and epitope structure.

Cross-reactivities between the major grass pollen allergens, at the level of T-cell recognition was examined employing several Lolium perenne I (Lol p I)-specific human T-cell clones. Nine of these Lol p I-specific T-cell clones exhibited cross-recognition of the recombinant Poa pratensis IX (Poa p IX) allergen, rKBG7.2, indicating that these two major antigens of a grass pollen share T-cell epitopes. Furthermore, proliferative responses of two other T-cell clones demonstrated that individual allergens of diverse grass pollens also possess common T-cell epitopes. Examination of the T-cell receptor (TcR) V alpha genes of these T-cell clones indicated that these cloned cells utilized distinct J alpha genes and that nine out of 10 clones possessed V alpha 13 gene. Furthermore, sequence comparisons of several allergenic molecules indicated that this cross-reactivity may be due to the presence of epitope(s) with structure(s) similar to the major T-cell epitope of Poa p IX allergens. Taken together, these results suggest for the first time that the major grass pollen allergens share cross-reacting T-cell epitope(s), and that this cross-reactivity is due to the structural homologies among allergens and restricted usage of TcR V alpha genes.

Allergens↗
PubMed1993

Serum levels of soluble interleukin-2 receptor in Hodgkin disease. Relationship with clinical stage, tumor burden, and treatment outcome.

BACKGROUND: Previous studies suggested a possible role for the detection of soluble interleukin-2 receptor (sIL-2R) in Hodgkin disease (HD). In this study, the authors investigated, in a large series of patients, sIL-2R serum levels in relation to disease features at presentation and prognosis. Their usefulness as markers in the management of individual cases was evaluated. METHODS: The sIL-2R serum levels were measured in 195 patients at diagnosis. In 72 of these patients, sIL-2R serum levels were also monitored after diagnosis. An additional 87 cases were tested only in complete remission (CR), and 25 were tested only at relapse. RESULTS: The sIL-2R levels at diagnosis were increased (mean +/- 1222 +/- 1012 versus 331 +/- 145 U/ml in controls, P < 0.0001) and correlated with the stage and tumor burden (Stages I and II = 1058 +/- 1007, Stages III and IV = 1502 +/- 942 U/ml, P = 0.003; Stage A = 954 +/- 705, Stage B = 1880 +/- 1238 U/ml, P < 0.0001; bulky presentation = 1958 +/- 1430, nonbulky presentation = 1043 +/- 791 U/ml, P < 0.0001). Response to treatment was associated with progressive reduction of sIL-2R levels, which were normal in virtually all cases 1 year after CR. Significantly greater levels at diagnosis were found in 11 patients who experienced a poor response or progression after treatment (P = 0.004). Overall, abnormal data in CR were found in 59 of 159 patients and 9 of them subsequently experienced a relapse. CONCLUSIONS: The sIL-2R serum levels in HD correlate with features at presentation and subsequent clinical courses. Higher levels at diagnosis entail a significantly higher risk of treatment failure.

Adolescent↗
PubMed1993

Membrane tumour necrosis factor-alpha is involved in the polyclonal B-cell activation induced by HIV-infected human T cells.

Infection of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.

Animals↗
PubMed1993

Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.

The effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (IL-12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of IL-12 exhibited reduced ability to produce IL-4 and increased ability to produce interferon gamma (IFN-gamma), and developed into Der p I-specific CD4+ T cell clones showing a T helper type 0 (Th0)- or Th1-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-IL-12 antibody exhibited an increased ability to produce IL-4 and developed into PPD-specific CD4+ T cell clones showing a Th0-, instead of Th1-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti-IFN-gamma antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16+ cells. Thus, IL-12 and CD16+ cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Th1-like responses.

Animals↗
PubMed1993

Identification of multiple T cell epitopes on Bet v I, the major birch pollen allergen, using specific T cell clones and overlapping peptides.

Eleven T cell clones (TCC) with specificity for Bet v I were established from the peripheral blood of six birch pollen allergic donors. Bet v I is the major allergen of birch (Betula verrucosa) pollen and shows high homology to the major allergens of pollens of other trees within the order fagales (hazel, alder, hornbeam, oak, etc.), which represent important inhalant allergens in the northern hemisphere. The TCC were shown to react with purified natural, as well as with purified recombinant Bet v I. All clones showed the helper cell phenotype (CD3+CD4+) and expressed the TCR-alpha/beta. The cytokine production pattern in response to stimulation with allergen resulted in enhanced production of IL-4 in 9 of 11 clones. The clones were used for T cell epitope mapping on the Bet v I molecule. For this purpose, peptides with a length of 12 amino acids each and overlapping for 10 residues were synthesized following the amino acid sequence of Bet v I. These 75 peptides were used to stimulate Bet v I-specific T cell clones. Our experiments revealed 7 distinct T cell epitopes on the Bet v I molecule. The epitopes were scattered over the whole molecule, 2 sequences were in agreement with an algorithm previously described for the prediction of T cell epitopes. In 3 cases, we could identify distinct TCC specificities within single individuals. Furthermore, for each donor, none of the peptides representing epitopes for TCC inhibited the binding of IgE antibodies to Bet v I. These results suggest that T cells and IgE antibodies from the same individual recognize different structures on the Bet v I allergen.

Allergens↗
PubMed1993

Abnormal B cell helper activity by virus-infected human CD4+ T cells.

Human CD4+ T cell clones infected in vitro with the human immunodeficiency virus (HIV), unlike their noninfected counterparts, induced both proliferation and immunoglobulin (Ig) production by both autologous and allogeneic B cells through an antigen (Ag)-nonspecific, MHC-unrestricted, contact-dependent mechanism. This was done apparently without expressing the CD40 ligand. Interestingly, HIV-infected T cell clones, unlike their noninfected counterparts, constitutively expressed mRNA for, and released in the supernatants measurable amounts of, TNF-alpha and a proportion of T blasts from the HIV-infected unstimulated T cell clones showed membrane TNF-alpha expression. Furthermore, both B cell proliferation and Ig production induced by HIV-infected unstimulated T cell clones, but not those evoked by their noninfected anti-CD3-stimulated counterparts, were strongly and consistently inhibited by either anti-TNF-alpha or anti-TNF-alpha receptor antibodies. Finally, when T blasts from HIV-infected unstimulated T cell clones were fractionated by cell sorting into membrane TNF-alpha-negative and membrane TNF-alpha-positive cells, only the latter retained the capacity to polyclonally activate B cells. Human CD4+ T cell clones infected in vitro with herpesvirus saimiri (HVS) also showed constitutive membrane TNF-alpha expression, as well as the ability to induce Ag-nonspecific, MHC-unrestricted, contact-dependent, polyclonal B cell activation. These data suggest that human CD4+ T cell clones, when infected by certain viruses, can provide abnormal B cell help that appears to be related to the expression of membrane TNF-alpha by virus-infected T cells.

B-Lymphocytes↗