scholarly journals Differences in the Frequency of Cytokine-Producing Cells in Antigenemic and Nonantigenemic Individuals with Bancroftian Filariasis

1998 ◽  
Vol 66 (4) ◽  
pp. 1377-1383 ◽  
Author(s):  
Adriana B. de Almeida ◽  
Maria Carmelita Maia e Silva ◽  
Cynthia Braga ◽  
David O. Freedman
Keyword(s):  
Lymphatic Filariasis ◽  
Mononuclear Cells ◽  
Intracellular Cytokine Staining ◽  
Clinical Manifestations ◽  
Wuchereria Bancrofti ◽  
Interleukin 4 ◽  
Bancroftian Filariasis ◽  
Peripheral Blood Mononuclear ◽  
Geometric Means ◽  
Ifn Γ

ABSTRACT Individuals with clinical manifestations of lymphatic filariasis may be currently infected or not. Twenty-five individuals from aWuchereria bancrofti-endemic area of Brazil were classified as being asymptomatic microfilaremic individuals, antigenemic individuals with clinical filariasis, or nonantigenemic individuals with clinical filariasis. Intracellular cytokine staining of mitogen-stimulated peripheral blood mononuclear cells (PBMC) showed that the frequency of either gamma interferon (IFN-γ)- or interleukin-4 (IL-4)-producing cells was higher in the nonantigenemic individuals with clinical filariasis than in the asymptomatic microfilaremic individuals (geometric means, 22.1 versus 10.7% [P = 0.02] and 2.9 versus 1.4% [P= 0.01], respectively). When the asymptomatic microfilaremic individuals and antigenemic individuals with clinical filariasis were grouped together to constitute all actively infected individuals, the frequency of IFN-γ-producing cells was also lower than in the nonantigenemic individuals with clinical filariasis (P= 0.04). Likewise, the frequency of IL-4-producing cells in the actively infected individuals was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.02). No differences in the frequency of IFN-γ-, IL-4-, or IL-5-producing cells in purified CD4 T lymphocytes were found among the groups. These findings suggest that the presence of antigenemia, which is an indicator of current active infection, is closely associated with the frequency of IFN-γ- and IL-4-producing cells in lymphatic filariasis. The differences found in the frequency of cytokine-producing cells among the three groups appear to be due to a subset of cells other than CD4 T cells.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

scholarly journals Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis

2004 ◽  
Vol 72 (5) ◽  
pp. 2598-2604 ◽  
Author(s):  
Suba Nookala ◽  
Sundaram Srinivasan ◽  
Perumal Kaliraj ◽  
Rangarajan Badri Narayanan ◽  
Thomas B. Nutman
Keyword(s):  
Immune Response ◽  
Lymphatic Filariasis ◽  
Proliferative Response ◽  
Wuchereria Bancrofti ◽  
Peripheral Blood Mononuclear ◽  
Lower Baseline ◽  
Tetanus Vaccination ◽  
Ifn Γ ◽  
Humoral Responses ◽  
Endemic Normal

ABSTRACT To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-γ) response in the EN group, in that they increased IFN-γ production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-γ responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10.

scholarly journals Contribution of CD8+ T Cells to Gamma Interferon Production in Human Tuberculosis

2001 ◽  
Vol 69 (5) ◽  
pp. 3497-3501 ◽  
Author(s):  
Homayoun Shams ◽  
Benjamin Wizel ◽  
Stephen E. Weis ◽  
Buka Samten ◽  
Peter F. Barnes
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Peripheral Blood Mononuclear ◽  
Tuberculosis Patients ◽  
Ifn Γ ◽  
Stimulation Of

ABSTRACT The proportions of peripheral blood mononuclear cells (PBMC), CD4+ T cells, and CD8+ T cells that produce gamma interferon (IFN-γ) in response to Mycobacterium tuberculosis were markedly reduced in tuberculosis patients, particularly in those with severe disease. Depletion of CD4+ but not CD8+ cells prior to stimulation of PBMC with M. tuberculosis abolished IFN-γ production. These results show that (i) IFN-γ production by CD8+ and CD4+ cells correlates with the clinical manifestations ofM. tuberculosis infection and (ii) IFN-γ production by CD8+ cells depends on CD4+ cells.

scholarly journals Cytokine Profiles of Patients Infected with Mycobacterium ulcerans and Unaffected Household Contacts

2002 ◽  
Vol 70 (10) ◽  
pp. 5562-5567 ◽  
Author(s):  
Travis M. Gooding ◽  
Paul D. R. Johnson ◽  
May Smith ◽  
Andrew S. Kemp ◽  
Roy M. Robins-Browne
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Household Contacts ◽  
Control Subjects ◽  
Cytokine Profiles ◽  
Ifn Γ

ABSTRACT Mycobacterium ulcerans, the cause of Buruli ulcer, is an environmental mycobacterium with a distinct geographic distribution. The reasons why only some individuals who are exposed to M. ulcerans develop ulcers are not known but are likely to reflect individual differences in the immune response to infections with this bacterium. In this study, we investigated cytokine profiles of peripheral blood mononuclear cells (PBMC) from 23 Buruli ulcer patients and 25 household contacts in a region of Australia where Buruli ulcer is endemic. The results showed that following stimulation with M. ulcerans or Mycobacterium bovis BCG, PBMC from Buruli ulcer patients mounted a Th2-type response, which was manifested by the production of mRNA for interleukin 4 (IL-4), IL-5, IL-6, and IL-10, whereas unaffected contacts responded mainly with the Th1 cytokines gamma interferon (IFN-γ) and IL-12. For example, mRNA for IL-4 was detected in 18 of 23 patients but in only 3 of 25 control subjects (P < 0.0001). By contrast, PBMC from 21 of 25 unaffected individuals produced IFN-γ compared with 3 of 23 patients (P < 0.0001). IFN-γ release following stimulation with mycobacteria was markedly reduced in affected subjects. Frequencies of antibodies to M. ulcerans in serum samples from affected and unaffected subjects were similar, indicating that many of the control subjects had been exposed to this bacterium. Together, these findings suggest that a Th1-type immune response to M. ulcerans may prevent the development of Buruli ulcer in people exposed to M. ulcerans, but a Th-2 response does not.

scholarly journals Cytokine Profiles in Adult Mink Infected with Aleutian Mink Disease Parvovirus

2003 ◽  
Vol 77 (13) ◽  
pp. 7444-7451 ◽  
Author(s):  
P. V. Jensen ◽  
Y. Castelruiz ◽  
B. Aasted
Keyword(s):  
Gamma Globulin ◽  
Mononuclear Cells ◽  
High Plasma ◽  
Interleukin 4 ◽  
Immune Functions ◽  
Peripheral Blood Mononuclear ◽  
Double Labeling ◽  
Virus Challenge ◽  
A Cell ◽  
Ifn Γ

ABSTRACT The aim of this study was to examine the levels of gamma interferon (IFN-γ)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8+) cells in the blood during the infection. We quantified the percentages of IFN-γ- and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-γ- and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-γ and IL-4 in ADV-infected mink was produced by CD8+ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1- and Th2-driven immune functions are found in mink plasmacytosis.

scholarly journals Immunization with Brucella VirB Proteins Reduces Organ Colonization in Mice through a Th1-Type Immune Response and Elicits a Similar Immune Response in Dogs

2014 ◽  
Vol 22 (3) ◽  
pp. 274-281 ◽  
Author(s):  
Cora N. Pollak ◽  
María Magdalena Wanke ◽  
Silvia M. Estein ◽  
M. Victoria Delpino ◽  
Norma E. Monachesi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Type Iv ◽  
Ifn Γ ◽  
Organ Colonization

ABSTRACTVirB proteins fromBrucellaspp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice fromBrucellainfection and whether this response can be induced in the dog, a natural host forBrucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with liveBrucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals uponin vitrostimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane ofBrucellaorganisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis ofB. caniswas assessedin vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization byBrucellain mice can be also elicited in dogs.

scholarly journals Leishmania pifanoi Amastigote Antigen P-4: Epitopes Involved in T-Cell Responsiveness in Human Cutaneous Leishmaniasis

1998 ◽  
Vol 66 (7) ◽  
pp. 3100-3105 ◽  
Author(s):  
Jessica E. Haberer ◽  
Alda Maria Da-Cruz ◽  
Lynn Soong ◽  
Manoel P. Oliveira-Neto ◽  
Luis Rivas ◽  
...  
Keyword(s):  
T Cell ◽  
Cutaneous Leishmaniasis ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Vaccine Development ◽  
Stimulation Index ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT In experimental murine cutaneous leishmaniasis, the purifiedLeishmania pifanoi amastigote protein P-4 has been shown to induce significant protection against infection. Further, recent studies examining the response of peripheral blood mononuclear cells (PBMC) from Leishmania braziliensis-infected human patients have demonstrated that the P-4 protein selectively elicits a significant TH1-like response. Because a TH1-like response is associated with cure, epitope studies were conducted to further evaluate the human response to P-4. PBMC from confirmed cutaneous leishmaniasis patients infected withL. braziliensis in Rio de Janeiro, Brazil, an area where the disease is endemic, were examined for T-cell proliferation and/or cytokine production in response to whole-parasite homogenate, isolated P-4 protein, and/or P-4 peptides. Twenty of the 22 patients (91%) examined responded to the native P-4 protein by proliferation and/or gamma interferon (IFN-γ) production. According to the proliferation data, PBMC from 14 patients (64%) were found to respond to the intact P-4 protein (stimulation index of ≥2.5). Fifty-seven percent of the P-4-responsive patients studied responded to at least one of the P-4 peptides; 11 individual peptides were found to elicit a proliferative response. Of 17 patients examined for cytokine production, no PBMC produced detectable interleukin-4 in response to P-4 protein or peptides. However, PBMC from 14 patients (82%) produced significant levels of IFN-γ (≥20 pg/ml) in response to native P-4 protein. Nineteen of the 23 peptides were found to elicit an IFN-γ response from at least two patients. These data indicate that multiple epitopes spanning the entire P-4 molecule are responsible for the TH1-like immune response observed, indicating that the intact P-4 amastigote molecule, rather than selected peptides, may prove to be the most useful for leishmaniasis vaccine development.

scholarly journals Protection of Rhesus Macaques against Lethal Plasmodium knowlesi Malaria by a Heterologous DNA Priming and Poxvirus Boosting Immunization Regimen

2002 ◽  
Vol 70 (8) ◽  
pp. 4329-4335 ◽  
Author(s):  
William O. Rogers ◽  
Walter R. Weiss ◽  
Anita Kumar ◽  
João C. Aguiar ◽  
John A. Tine ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Plasmodium Knowlesi ◽  
Rhesus Macaques ◽  
Geometric Mean ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Vaccine Regimen ◽  
Macaque Model ◽  
Ifn Γ

ABSTRACT We tested a cytokine-enhanced, multiantigen, DNA priming and poxvirus boosting vaccine regimen for prevention of malaria in the Plasmodium knowlesi-rhesus macaque model system. Animals were primed with a mixture of DNA plasmids encoding two preerythrocytic-stage proteins and two erythrocytic-stage proteins from P. knowlesi and combinations of the cytokines granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor alpha and were boosted with a mixture of four recombinant, attenuated vaccinia virus strains encoding the four P. knowlesi antigens. Two weeks after boosting, the geometric mean immunofluorescence titers in the immunized groups against sporozoites and infected erythrocytes ranged from 160 to 8,096 and from 1,810 to 5,120, respectively. The geometric mean anti-P. knowlesi circumsporozoite protein (PkCSP) titers ranged from 1,761 to 24,242. Peripheral blood mononuclear cells (PBMC) from the immunized monkeys produced gamma interferon (IFN-γ) in response to incubation with pooled peptides from the PkCSP at frequencies of 10 to 571 spot-forming cells/106 PBMC. Following challenge with 100 infectious P. knowlesi sporozoites, 2 of 11 immunized monkeys were sterilely protected, and 7 of the 9 infected monkeys resolved their parasitemias spontaneously. In contrast, all four controls became infected and required treatment for overwhelming parasitemia. Early protection was strongly associated with IFN-γ responses against a pool of peptides from the preerythrocytic-stage antigen, PkCSP. These findings demonstrate that a multistage, multiantigen, DNA priming and poxvirus boosting vaccine regimen can protect nonhuman primates from an otherwise lethal malaria sporozoite challenge.

scholarly journals Increased Levels of Alternatively Spliced Interleukin 4 (IL-4δ2) Transcripts in Peripheral Blood Mononuclear Cells from Patients with Systemic Sclerosis

1999 ◽  
Vol 6 (5) ◽  
pp. 660-664 ◽  
Author(s):  
Lazaros I. Sakkas ◽  
Charles Tourtellotte ◽  
Steve Berney ◽  
Allen R. Myers ◽  
Chris D. Platsoucas
Keyword(s):  
Systemic Sclerosis ◽  
Mononuclear Cells ◽  
Full Length ◽  
Interleukin 4 ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Blood Mononuclear Cells ◽  
Alternatively Spliced ◽  
Ifn Γ

ABSTRACT Recent in vitro studies have shown that interleukin 4 (IL-4) induces and gamma interferon (IFN-γ) inhibits collagen production. To define the TH1(IFN-γ) and TH2(IL-4) cytokine profiles in systemic sclerosis (Sscl), a disease characterized by widespread fibrosis, we investigated IL-4 and IFN-γ transcripts in peripheral blood mononuclear cells and plasma protein levels in 13 patients with Sscl. Two previously identified IL-4 transcripts, a full-length transcript and an alternatively spliced (truncated) transcript (designated IL-4δ2), were identified in patients and normal controls. Significantly increased levels of total IL-4 transcripts (full-length plus IL-4δ2 transcripts) were found in patients with Sscl in comparison to those found in healthy controls (P = 0.003), and this increase was primarily due to an increase in the level of the alternatively spliced IL-4δ2 form. The IL-4δ2/full-length-IL-4 transcript ratio was significantly increased in Sscl patients (P < 0.0001, versus healthy controls). Sequencing analysis revealed that the frequency of IL-4 clones carrying the IL-4δ2 transcript was also substantially increased in patients with Sscl. Plasma IL-4 protein levels were increased in Sscl patients compared to those in healthy controls (P = 0.001) and correlated with total IL-4 transcript levels. The up-regulation of the fibrogenic IL-4 (a TH2 cytokine) in Sscl suggests a pathogenic role for IL-4 in this disease.

scholarly journals Differential Production of Systemic and Intralesional Gamma Interferon and Interleukin-10 in Nodular and Ulcerative Forms of Buruli Disease

2004 ◽  
Vol 72 (2) ◽  
pp. 958-965 ◽  
Author(s):  
Ghislaine Prévot ◽  
Eliane Bourreau ◽  
Herve Pascalis ◽  
Roger Pradinaud ◽  
Audrey Tanghe ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Detection Threshold ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Mycobacterium Ulcerans ◽  
Interleukin 4 ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Buruli disease, caused by Mycobacterium ulcerans, is the third most important mycobacterial disease in humans besides tuberculosis and leprosy. We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease. Gamma interferon (IFN-γ) levels in response to whole M. ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts. Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures. IFN-γ production after stimulation with M. ulcerans was significantly lower (P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules. On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response to M. ulcerans (but not to M. bovis BCG) and production was highest in patients with the ulcerative form. Third, semiquantitative reverse transcription-PCR analysis demonstrated a similar difference in the local, intralesional cytokine profile for the two forms of the disease: high IFN-γ but low IL-10 mRNA levels in nodular lesions and high IL-10 but low IFN-γ mRNA levels in ulcerative lesions. Intralesional IL-4 and IL-13 mRNA levels were low and only detected in patients with the ulcerative form. Our results indicate, although they do not formally prove, that production of IL-10 rather than production of IL-4 or IL-13 by Th2-type T cells may be involved in the low M. ulcerans-specific IFN-γ response in Buruli disease patients.

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