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3.
Int J Immunopathol Pharmacol ; 24(1): 231-8, 2011.
Article in English | MEDLINE | ID: mdl-21496407

ABSTRACT

Natural killer (NK) cells play a fundamental role in innate and early phases of adaptive immunity against viral infections, both in humans and in animal models. To date, NK cell deficiencies in patients with severe herpetic infections have been reported in single cases, and their role as predisposing factor is still controversial. Five children affected by herpetic encephalitis were consecutively admitted to the Anna Meyer Children's Hospital in Florence (Italy) between 2003 and 2005. We therefore investigated the presence of NK cell deficiencies in a consecutive series of children with herpetic encephalitis. Five healthy children were included in the study as controls. Differential WBC counts, main Ig and IgE class serum analysis, cytofluorimetric analysis of circulating T, B and NK cells were performed on our study population. Sequencing of a selected region of CD16A gene transcript was carried out in two patients. All patients resulted to be affected by deficiencies related to NK cells in respect to controls. One patient was also affected by lymphopenia, while no other significant deficits of immunity were detected in the study population. To date, this is the first survey that demonstrates isolated NK cell deficiencies in a cohort of consecutive patients affected by severe herpes simplex infections. These findings suggest a role for NK cell deficiencies as a predisposing factor for increased susceptibility and severe course of disease in these patients.


Subject(s)
Encephalitis, Herpes Simplex/immunology , Killer Cells, Natural/immunology , Child , Child, Preschool , Female , Flow Cytometry , Humans , Immunoglobulins/blood , Infant , Infant, Newborn , Leukocyte Count , Lymphocyte Subsets , Male , Receptors, IgG/genetics
4.
Eur Ann Allergy Clin Immunol ; 37(9): 343-4, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16453966

ABSTRACT

We report the case of an atopic male, 76 years old, with post-myocardial infarction ischaemic cardiopathy, arterial hypertension and a history of insect-sting induced large local reactions who died because of a biphasic anaphylaxis subsequent to multiple Vespid stings (about 15). Within approximately ten minutes after the stings he developed urticaria, extended erythema and hypotension (90/60 mmHg), measured by a family member. The objective physical examination by the emergency doctor at the patient's home revealed an orticarioid reaction and erythema of the back and neck, an unaffected respiratory apparatus and CNS, normal pupils, a pulse rate of 74, normal blood pressure ranging from 120/70 to 130/60 mmHg. The patient was administered antihistamine and corticosteroid through parenteral route. During the 45' observation period at the patient's home the urticaria subsided but not to completion. Approximately 40 minutes after the emergency doctor left, the urticaria reoccurred, angioedema of the neck and worsening asthenia developed. The patient died, despite attempts to resuscitate him by the emergency doctor that had been called out again. A post-mortem examination revealed generalised eodema of the lungs, brain, glottis, and bowels due to the severe characteristic systemic compromise of anaphylaxis. The Authors discuss whether an early use of adrenalin and/or a longer observation time could have saved the patient.


Subject(s)
Anaphylaxis/drug therapy , Anaphylaxis/etiology , Epinephrine/administration & dosage , Insect Bites and Stings/complications , Wasp Venoms/adverse effects , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Aged , Ambulatory Care/standards , Angioedema/etiology , Animals , Fatal Outcome , Heart Diseases/complications , Histamine H1 Antagonists/administration & dosage , Humans , Hypertension/complications , Male , Time Factors , Urticaria/etiology
6.
Am J Hypertens ; 14(3): 259-66, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11281238

ABSTRACT

BACKGROUND: Increased expression of the endothelial leukocyte adhesion molecule E-selectin is implicated in vascular disease and may accompany the development of hypertension. We evaluated plasma soluble (s) E-selectin to assess its relationship with endothelium-dependent and endothelium-independent vasodilation in patients with hypertension. METHODS: Thirty-one previously untreated and uncomplicated essential hypertensive patients were compared with 16 normotensive controls for changes in forearm blood flow (by strain-gauge plethysmography) in response to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine, and of the endothelium-independent vasodilator sodium nitroprusside. As an index of structural changes, minimal forearm vascular resistances were calculated as the ratio between maximal vasodilation after 13 min of ischemia and mean blood pressure. RESULTS: Responses to acetylcholine were significantly lower and minimal forearm vascular resistances higher in hypertensives versus controls, whereas responses to nitroprusside were comparable. Baseline sE-selectin concentrations were (mean +/- SEM) 37.4 +/- 1.8 ng/mL in hypertensives and 27.8 +/- 0.7 ng/mL in normotensives (P < .001). In essential hypertensive patients, a significant (P < .01) correlation with the response to nitroprusside (r = -0.47) was found, but not with the response to acetylcholine or minimal forearm vascular resistances. sE-selectin was also positively correlated with age and LDL cholesterol. At multivariate analysis, sE-selectin remained significantly correlated with nitroprusside responses and LDL cholesterol. CONCLUSIONS: In patients with essential hypertension, plasma levels of sE-selectin are higher than in normotensive controls and mostly related to structural vascular changes.


Subject(s)
E-Selectin/blood , Hypertension/blood , Hypertension/physiopathology , Vasomotor System/physiology , Acetylcholine/pharmacology , Female , Forearm/blood supply , Humans , Male , Middle Aged , Nitroprusside/pharmacology , Plethysmography , Vascular Resistance/physiology
7.
Clin Immunol ; 91(3): 338-44, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10370380

ABSTRACT

It is essential to distinguish the role of T lymphocytes on the physiopathology associated to more severe forms of schistosomiasis and on the immunomodulation that evolves in the majority of infected people. In this study, we generated Schistosoma mansoni-specific T cell lines and clones from patients with the acute and chronic (intestinal and hepatosplenic forms) phases of disease, from former ones, and from uninfected individuals sensitized to parasite soluble antigens. T cell lines derived from nontreated acute infected donors were capable of producing IL-4 and IL-5, while cells from treated patients secreted IFN-gamma. Lines from intestinal chronic and antigen-sensitized donors preferentially produced IFN-gamma, while those from hepatosplenic patients secreted all three cytokines. The cytokine analysis of CD4+ T cell clones revealed a Th2/Th0 pattern (clones producing IL-4 and IL-5 and clones producing all three cytokines) for those derived from infected patients, while cells from antigen-sensitized donors exhibited an opposite Th1/Th0 pattern (clones producing IFN-gamma and clones producing all three cytokines). The possible role of these T cell populations on human schistosomiasis mansoni is discussed.


Subject(s)
Cytokines/biosynthesis , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , T-Lymphocytes/immunology , Acute Disease , Animals , Antigens, Helminth/administration & dosage , Cell Line , Chronic Disease , Clone Cells , Granuloma/immunology , Humans , Immunization , Lymphocyte Activation , Phenotype , Th1 Cells/immunology , Th2 Cells/immunology
8.
J Immunol ; 159(1): 206-13, 1997 Jul 01.
Article in English | MEDLINE | ID: mdl-9200456

ABSTRACT

The mRNA and protein expression of the alpha- and beta-chains of IFN-gammaR were evaluated on a panel of human Th1 and Th2 clones. When cultured in IL-2-conditioned medium, both types of clones expressed mRNA for the alpha- and beta-chains, and both chains were present in the cytoplasm. Membrane expression of the alpha-chain was higher on Th2 than on Th1, whereas the beta-chain was poorly expressed on both types but increased following IL-2 withdrawal or PHA stimulation. In addition, both types of clones overexpressed MHC class I glycoproteins following IFN-gammaR triggering by exogenous IFN-gamma, although the kinetics was slower in Th1, and this exposure induced mRNA for IRF-1. When their TCR was triggered in the absence of APC, Th1 only underwent apoptosis. This activation-induced apoptosis was prevented by blocking of the alpha-chain or by IFN-gamma neutralization. Addition of IFN-gamma triggered the apoptosis of Th2 clones. Apoptosis of both types of clones was mediated by autocrine or exogenous IFN-gamma through the up-regulation of Fas-L expression, since anti-IFN-gammaR alpha mAb inhibited its expression on Th1 and exogenous IFN-gamma increased its expression on Th2. These results indicate that activated human Th1 and Th2 lymphocytes express IFN-gammaR alpha- and beta-chains and are both sensitive to signals provided by IFN-gamma. Data also suggest that IFN-gamma is critical for switching off their responses.


Subject(s)
Apoptosis , Receptors, Antigen, T-Cell/metabolism , Receptors, Interferon/metabolism , Th1 Cells/pathology , Th2 Cells/pathology , Clone Cells , Humans , RNA, Messenger/analysis , Signal Transduction , Th1 Cells/metabolism , Th2 Cells/metabolism , Interferon gamma Receptor
9.
Eur J Immunol ; 27(7): 1751-5, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9247587

ABSTRACT

Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.


Subject(s)
Antigens, Bacterial , Cytokines/analysis , Epitopes/analysis , Gastritis/immunology , Helicobacter pylori/immunology , Peptic Ulcer/immunology , Pyloric Antrum/immunology , T-Lymphocytes/immunology , Adult , Bacterial Proteins/analysis , Chaperonin 60/analysis , Chronic Disease , Clone Cells , Female , Gastritis/microbiology , Humans , Male , Middle Aged , Peptic Ulcer/microbiology , Pyloric Antrum/microbiology , T-Lymphocytes/microbiology
11.
Immunol Lett ; 51(1-2): 83-8, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8811349

ABSTRACT

CD30 is a member of the tumor necrosis factor (TNF)-receptor superfamily, whose ligand (CD30L) has been identified on B cells, activated macrophages and a subset of activated T cells. We show here that infection in vitro with human immunodeficiency virus (HIV) of CD4+ T-cell clones generated from HIV-seronegative individuals can enhance the expression of CD30, which often preceeds and is associated with the death of clonal T cells. Furthermore, cross-linking CD30 with an agonistic CD30-specific monoclonal antibody potentiated HIV replication induced by an insolubilized anti-CD3 antibody in T-cell lines generated from HIV-infected individuals. More importantly, paraformaldehyde-fixed CD8+ T-cell clones expressing CD30L enhanced HIV replication in anti-CD3-stimulated allogeneic or autologous HIV-infected CD4+ T-cell lines and such a potentiating effect was inhibited by an anti-CD30L antibody. The anti-CD30L antibody also exerted a suppressive effect on the spontaneous HIV replication occurring in lymph node cells, freshly derived from an HIV-seropositive patient showing CD30 expression in B cells and in a proportion of CD8+ T lymphocytes. Thus, CD30 triggering may play an important role in both HIV replication and the death of HIV-infected CD4+ T cells.


Subject(s)
HIV/drug effects , Ki-1 Antigen/pharmacology , Virus Replication/drug effects , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/metabolism , CD30 Ligand , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/virology , Cell Death/immunology , Cell Line , HIV Infections/immunology , Humans , Ki-1 Antigen/immunology , Ki-1 Antigen/metabolism , Ligands , Membrane Glycoproteins/biosynthesis , Protein Binding/immunology
12.
Eur J Immunol ; 26(2): 329-34, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8617299

ABSTRACT

Omenn's syndrome (OS) is a severe immunodeficiency, characterized by clinical and laboratory features reminiscent of a T helper type-2 (Th2) response. CD30, a member of the tumor necrosis factor receptor superfamily, has been found to be preferentially expressed by human T cell clones exhibiting a Th2-line profile and function. We investigated whether there are derangement in CD30 expression in tissues, and/or abnormalities in soluble CD30 (sCD30) levels in the serum, or both, of three children with OS and one child with maternal engraftment and Omenn's-like syndrome (OLS). Large proportions of tissue-infiltrating T lymphocytes from all four patients expressed CD30, whereas in control tissues, including peripheral blood, CD30+ T lymphocytes were extremely few or absent. In addition, levels of sCD30 were abnormally increased in all patients' sera. T cell clones were generated from sorted CD30+ and CD30-peripheral blood T cells of the patient with OLS who showed unusually high numbers of circulating CD30+ T lymphocytes. Most CD4+ T cell clones derived from CD30+ cells showed a Th2-like cytokine profile, whereas the majority of clones generated from CD30-T cells were Th1. These findings support the hypothesis that Th2 cells are involved in the pathogenesis of OS. Moreover, they provide evidence that detection of CD30+ T cells in tissues, increased levels of sCD30 in biological fluids, or both, reflect the presence of immune responses characterized by prevalent activation of T cells producing Th2 cytokines.


Subject(s)
Ki-1 Antigen/blood , Severe Combined Immunodeficiency/immunology , Th2 Cells/immunology , Cytokines/biosynthesis , Female , Humans , Immunohistochemistry , Infant, Newborn , Ki-1 Antigen/biosynthesis , Ki-1 Antigen/immunology , Lymph Nodes/pathology , Male , Severe Combined Immunodeficiency/blood , Severe Combined Immunodeficiency/pathology , Solubility , Syndrome
14.
J Exp Med ; 182(6): 1655-61, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-7500010

ABSTRACT

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.


Subject(s)
Ki-1 Antigen/physiology , T-Lymphocyte Subsets/immunology , Th2 Cells/immunology , Antigen-Presenting Cells/physiology , CD30 Ligand , Cells, Cultured , Cytokines/metabolism , Humans , Immunologic Memory , Lymphocyte Activation , Membrane Glycoproteins/physiology , Signal Transduction
15.
Immunity ; 3(2): 251-5, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7648397

ABSTRACT

CD30 is a member of the tumor necrosis factor receptor superfamily, preferentially expressed by T cells producing type 2 helper (Th2) cytokines, whose ligand (CD30L) has been identified on B cells, activated macrophages, and a subset of activated T cells. We show here that cross-linking CD30 with an agonistic CD30-specific monoclonal antibody, as well as with CD30L+ CD8+ T cell clones or CD30L+ B cells, enhanced HIV replication in CD4+ T cells from HIV-infected individuals, and such a potentiating effect was inhibited by anti-CD30L antibody. The anti-CD30L antibody also exerted a suppressive effect on spontaneous HIV replication occurring in lymph node cells from an HIV-sero-positive patient, showing CD30L expression by both B and CD8+ T lymphocytes. Thus, CD30 triggering by CD30L-expressing cells may plan an important role in the activation of HIV expression from latently infected CD4+ T cells.


Subject(s)
CD4-Positive T-Lymphocytes/microbiology , HIV Infections/microbiology , HIV-1/growth & development , Ki-1 Antigen/physiology , Membrane Glycoproteins/physiology , Virus Replication , B-Lymphocytes/physiology , CD3 Complex/physiology , CD30 Ligand , CD8-Positive T-Lymphocytes/physiology , Cells, Cultured , Humans , Immunophenotyping , In Vitro Techniques , Signal Transduction
16.
FASEB J ; 9(1): 81-6, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7821763

ABSTRACT

A large panel of human CD4+ T helper (Th) cell clones with established Th1, Th2, or Th0 profiles of cytokine secretion were examined for the expression of CD30, a member of the tumor necrosis factor receptor superfamily. Th1 clones expressed poor or no CD30 mRNA, and showed low or undetectable expression of both membrane and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and membrane CD30 and released substantial amounts of sCD30. Th0 clones exhibited an intermediate pattern of CD30 expression and release. When T cells from the same donor were stimulated with three different antigens (purified protein derivative, PPD; Toxocara canis excretory/secretory antigen, TES; Lolium perenne group I, Lol p I), production of high concentrations of IFN-gamma, but not expression of CD30 or production of IL-4 and IL-5, were observed at any time after stimulation with PPD. In contrast, both CD30 expression and production of IL-4 and IL-5, but not of IFN-gamma, were concomitantly detectable in TES- and Lol p I-reactive T cells, suggesting a temporal relationship between CD30 expression and beginning of Th2-type cytokine production. Finally, CD4+CD30+ T cells specific for Lol p I and inducible to production of Th2-type cytokines were sorted out from the circulation of grass-sensitive patients in concomitance with the onset of allergic symptoms during the seasonal exposure to grass pollen. Thus, CD30 expression appears to be associated with the differentiation/activation pathway of human T cells producing Th2-type cytokines.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Cytokines/biosynthesis , Gene Expression , Ki-1 Antigen/genetics , T-Lymphocytes, Helper-Inducer/metabolism , Allergens/immunology , Antigens/immunology , CD4-Positive T-Lymphocytes/immunology , Humans , Kinetics , Lymphocyte Activation , Pollen/immunology
17.
J Immunol ; 153(11): 4872-9, 1994 Dec 01.
Article in English | MEDLINE | ID: mdl-7525717

ABSTRACT

We have shown that in vitro infection herpesvirus saimiri (HVS) can transform human CD4+ T cell clones with defined Th1 or Th2 cytokine profiles to continuous growth. We report here that transformation with HVS enabled both Th1 and Th2 clones to stimulate proliferation and Ig production by autologous or allogeneic B cells in the absence of stimulants. The polyclonal B cell-activating property of HVS-transformed clones was not related to free virus or soluble cytokines, but rather was dependent on an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. T blasts from unstimulated HVS-transformed clones did not express CD40 ligand (CD40L) mRNA or CD40L protein, whereas a proportion of them constitutively expressed membrane TNF (mTNF)-alpha. Both CD40L and mTNF-alpha were detectable on either uninfected or HVS-transformed clones upon mitogen stimulation. The activation of high-density B cells by unstimulated HVS-transformed clones was not inhibited by soluble CD40-Ig fusion protein, but was strongly reduced by either anti-TNF-alpha or anti-TNF-alpha receptor (TNF-alpha R) mAbs. Addition of anti-CD2 and/or anti-CD58 mAbs was also inhibitory, but no additive effect with anti-TNF-alpha and/or anti-TNF-alpha R mAbs was observed. Neither anti-IL-2 nor CD40-Ig inhibited the proliferation of naive IgD+ B cells cocultured with fixed unstimulated HVS-transformed clones, whereas a combination of anti-TNF-alpha and anti-TNF-alpha R mAbs was inhibitory. In addition, fixed unstimulated HVS-transformed clones induced Ig synthesis in IgD+ naive B cells even in the absence of exogenous IL-2. Data suggest that both the mTNF-alpha/TNF-alpha R and the CD2/CD58 pathways, but not the CD40L-CD40 interaction plus secreted cytokines, are involved in the unusual mode of B cell activation exerted by CD4+ HVS-transformed clones.


Subject(s)
B-Lymphocytes/immunology , Cell Transformation, Viral/immunology , Herpesvirus 2, Saimiriine/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Antibodies, Monoclonal/immunology , Antigens, CD/immunology , CD2 Antigens/immunology , CD58 Antigens , Cell Line, Transformed , Cell Transformation, Neoplastic/immunology , Clone Cells , Flow Cytometry , Humans , Lymphocyte Activation/immunology , Membrane Glycoproteins/immunology , Receptors, Tumor Necrosis Factor/immunology , Tumor Necrosis Factor-alpha/immunology
18.
Br J Cancer ; 69(6): 1065-71, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8198972

ABSTRACT

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.


Subject(s)
Adenoma/immunology , Adenoma/pathology , Growth Substances/pharmacology , Interleukin-6/biosynthesis , Parotid Neoplasms/immunology , Parotid Neoplasms/pathology , Actins/biosynthesis , Adenoma/ultrastructure , Cell Differentiation , Cell Division/drug effects , Cell Line , Epithelium/immunology , Epithelium/pathology , Epithelium/ultrastructure , Humans , Immunohistochemistry , Interleukin-6/analysis , Interleukin-6/pharmacology , Kinetics , Microscopy, Electron , Microscopy, Immunoelectron , Parotid Neoplasms/ultrastructure , Polymerase Chain Reaction/methods , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Receptors, Interleukin/metabolism , Receptors, Interleukin-6 , Tumor Cells, Cultured
19.
Semin Immunol ; 5(6): 449-55, 1993 Dec.
Article in English | MEDLINE | ID: mdl-8123798

ABSTRACT

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.


Subject(s)
B-Lymphocytes/physiology , HIV Infections/immunology , T-Lymphocytes, Helper-Inducer/physiology , Tumor Necrosis Factor-alpha/physiology , Cell Communication/immunology , Cells, Cultured , Herpesvirus 2, Saimiriine/physiology , Humans
20.
Nature ; 363(6428): 464-6, 1993 Jun 03.
Article in English | MEDLINE | ID: mdl-7684824

ABSTRACT

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.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Lymphocyte Activation , Tumor Necrosis Factor-alpha/immunology , Animals , Antibody Formation , Antigens, CD , Antigens, Differentiation, B-Lymphocyte , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/microbiology , CD40 Antigens , CD40 Ligand , Cells, Cultured , Goats , HIV , HIV Infections/pathology , HIV Seropositivity/immunology , Humans , Lymph Nodes/immunology , Lymph Nodes/pathology , Membrane Glycoproteins/biosynthesis , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis
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