scholarly journals Cellular and Cytokine Correlates of Mucosal Protection in Murine Model of Oral Candidiasis

2000 ◽  
Vol 68 (10) ◽  
pp. 5771-5777 ◽  
Author(s):  
Shokrollah Elahi ◽  
Gerald Pang ◽  
Robert Clancy ◽  
Robert B. Ashman
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Regional Lymph Node ◽  
Oral Candidiasis ◽  
T Cell Response ◽  
Interleukin 4 ◽  
Mouse Strains ◽  
Carriage Rate ◽  
Lymph Node Cells ◽  
Ifn Γ

ABSTRACT Host protection against Candida albicans infection in a model of oral candidiasis involving infection-prone [DBA/2 (H-2d )] and less infection-prone [BALB/c (H-2d )] mouse strains was analyzed in terms of antibody and cellular responses, and in terms of cytokine patterns from regional lymph node cells. There was a selective expansion of γ/δ+ T-cell receptor cells, which correlated with the patterns of colonization in both mouse strains, with higher numbers of γ/δ T cells detected in BALB/c mice. Antigen-induced T-cell proliferation was significantly higher in BALB/c mice than in DBA/2 mice. Higher levels of serum immunoglobulin G (IgG) and salivary IgA antibodies were detected in BALB/c mice than in DBA/2 mice, but only after the infection was cleared. The cervical lymph node cells from infected mice were assessed for interleukin-4 (IL-4), IL-12, and gamma interferon (IFN-γ) mRNA gene expression by reverse transcription-PCR and protein production in the culture supernatants following restimulation in vitro. In BALB/c mice, an early increase in levels of IL-4, IFN-γ, and IL-12 correlated with rapid elimination of C. albicans. In DBA/2 mice, where resolution of infection was delayed, IL-4 message expression was delayed and the IL-4 secretion level was lower. Neutralization of IL-4 by multiple injections of an anti-IL-4 monoclonal antibody in BALB/c mice resulted in increased carriage rate and delayed clearance of the yeasts. Collectively, the data suggest that the T-cell response to C. albicans in the regional lymph nodes which correlates best with rapid oral clearance ofC. albicans is a balanced Th0 cytokine response involving early secretion of both IFN-γ and IL-4.

scholarly journals Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node

2005 ◽  
Vol 202 (6) ◽  
pp. 771-781 ◽  
Author(s):  
Eileen T. Samy ◽  
Lucy A. Parker ◽  
Colin P. Sharp ◽  
Kenneth S.K. Tung
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Regional Lymph Node ◽  
T Cell Response ◽  
Disease Suppression ◽  
Continuous Control ◽  
Antigen Specificity ◽  
T Cell Suppression ◽  
Ifn Γ

This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-γ production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.

scholarly journals T-cell recognition of human haemoglobin. Localization of the full T-cell recognition profile of the β-chain by a comprehensive synthetic strategy

1986 ◽  
Vol 234 (2) ◽  
pp. 449-452 ◽  
Author(s):  
M Yoshioka ◽  
N Yoshioka ◽  
M Z Atassi
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
Mouse Strains ◽  
Cell Recognition ◽  
Beta Chain ◽  
Human Haemoglobin ◽  
T Cell Recognition ◽  
Lymph Node Cells

This paper reports the localization of the regions on the beta-chain that are recognized by T cells from mice immunized with haemoglobin. The 14 overlapping peptides encompassing the entire beta-chain were examined in vitro for their ability to stimulate lymph-node cells from haemoglobin-primed B10.D2 (H-2d) and SJL (H-2s) mice. Several regions of the molecule (T sites) were found to stimulate haemoglobin-primed lymph-node cells. This strategy has enabled the localization of the full profile of T-cell recognition of the beta-chain by these mouse strains. Some of the regions that stimulated T cells appeared to coincide with those recognized by antibodies (i.e. B cells). It is noteworthy that, in addition to sites recognized by both T and B cells, the protein has other sites that are recognized exclusively by T cells and to which no detectable antibody response is directed.

scholarly journals Cytokine Induction by Streptococcus mutans and Pulpal Pathogenesis

2000 ◽  
Vol 68 (12) ◽  
pp. 6785-6789 ◽  
Author(s):  
Chin-Lo Hahn ◽  
Al M. Best ◽  
John G. Tew
Keyword(s):  
T Cells ◽  
T Cell ◽  
Streptococcus Mutans ◽  
Plasma Cells ◽  
Mrna Level ◽  
T Cell Response ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Chronic pulpal inflammation under caries appears to be elicited by bacterial antigens that diffuse into the pulp through dentinal tubules. This prompted the hypothesis that cytokines elicited by antigens fromStreptococcus mutans, which frequently dominates shallow lesions, could play a major role in eliciting the initial T-cell response in the pulp. To test this, we examined the ability of S. mutans to stimulate T cells and elicit cytokines and usedLactobacillus casei, which often predominates in deep carious lesions where B cells and plasma cells predominate, as a control. In addition, the presence of cytokines in the pulp was analyzed at the mRNA level. S. mutans elicited potent gamma interferon (IFN-γ) responses in peripheral blood mononuclear cell cultures and reduced the CD4/CD8 ratio by promoting CD8+ T cells. Multiple inflammatory cytokine mRNAs (IFN-γ, interleukin 4 [IL-4], and IL-10) were detected in human dental pulp. A higher prevalence of IFN-γ (67%) than IL-4 (19%) or IL-10 (29%) was obtained in shallow caries, suggesting a type 1 cytokine mechanism in early pulpitis where S. mutanspredominates. In contrast, in deep caries no differences in cytokine frequency were observed. Furthermore, the presence of IFN-γ in the pulp correlated with the presence of S. mutans. The extraordinary induction of type 1 cytokines and the preferential activation of CD8+ T cells by S. mutans offers an explanation for the etiology of the CD8+ T-cell-dominant lesion in early pulpitis and suggests that S. mutans may have a major impact on the initial lesion and pulpal pathology.

scholarly journals Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

2011 ◽  
Vol 209 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Ikuko Ueki ◽  
Norio Abiru ◽  
Kentaro Kawagoe ◽  
Yuji Nagayama
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Recombinant Adenovirus ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Tsh Receptor ◽  
Mouse Strains ◽  
Susceptible Mouse ◽  
Ifn Γ

Experimental Graves'-like hyperthyroidism can be induced in susceptible mouse strains by repetitive immunizations with recombinant adenovirus expressing the human full-length TSH receptor (TSHR) or its A-subunit. Previous studies have shown that splenocytes from immunized mice produce interferon (IFN)-γ and interleukin (IL) 10 in response to antigen stimulation in an in vitro T cell recall assay. Although IFN-γ is now well known to be essential for disease induction, the role(s) played by IL10 are unknown. Therefore, this study was conducted to clarify the significance of endogenous IL10 in the pathogenesis of experimental Graves' disease using IL10 deficient (IL10−/−) mice. Our results show that T cell response was augmented when estimated by their antigen-specific secretion of the key cytokine IFN-γ, but B cell function was dampened, that is, anti-TSHR antibody titers were decreased in IL10−/− mice, resulting in a lower incidence of Graves' hyperthyroidism (54% in IL10+/+ vs 25% in IL10−/−). Thus, in addition to IFN-γ, these data clarified the role of IL10 for optimizing anti-TSHR antibody induction and eliciting Graves' hyperthyroidism in our Graves' mouse model.

scholarly journals Neonatal Exposure to a Self-Peptide–Immunoglobulin Chimera Circumvents the Use of Adjuvant and Confers Resistance to Autoimmune Disease by a Novel Mechanism Involving Interleukin 4 Lymph Node Deviation and Interferon γ–mediated Splenic Anergy

1998 ◽  
Vol 188 (11) ◽  
pp. 2007-2017 ◽  
Author(s):  
Booki Min ◽  
Kevin L. Legge ◽  
Christopher Pack ◽  
Habib Zaghouani
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Proteolipid Protein ◽  
Interleukin 4 ◽  
Target Cells ◽  
Newborn Mice ◽  
Ifn Γ ◽  
Specific Regulation

Induction of neonatal T cell tolerance to soluble antigens requires the use of incomplete Freund's adjuvant (IFA). The side effects that could be associated with IFA and the ill-defined mechanism underlying neonatal tolerance are setbacks for this otherwise attractive strategy for prevention of T cell–mediated autoimmune diseases. Presumably, IFA contributes a slow antigen release and induction of cytokines influential in T cell differentiation. Immunoglobulins (Igs) have long half-lives and could induce cytokine secretion by binding to Fc receptors on target cells. Our hypothesis was that peptide delivery by Igs may circumvent the use of IFA and induce neonatal tolerance that could confer resistance to autoimmunity. To address this issue we used the proteolipid protein (PLP) sequence 139–151 (hereafter referred to as PLP1), which is encephalitogenic and induces experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. PLP1 was expressed on an Ig, and the resulting Ig–PLP1 chimera when injected in saline into newborn mice confers resistance to EAE induction later in life. Mice injected with Ig–PLP1 at birth and challenged as adults with PLP1 developed T cell proliferation in the lymph node but not in the spleen, whereas control mice injected with Ig–W, the parental Ig not including PLP1, developed T cell responses in both lymphoid organs. The lymph node T cells from Ig–PLP1 recipient mice were deviated and produced interleukin (IL)-4 instead of IL-2, whereas the spleen cells, although nonproliferative, produced IL-2 but not interferon (IFN)-γ. Exogenous IFN-γ, as well as IL-12, restored splenic proliferation in an antigen specific manner. IL-12–rescued T cells continued to secrete IL-2 and regained the ability to produce IFN-γ. In vivo, administration of anti–IL-4 antibody or IL-12 restored disease severity. Therefore, adjuvant-free induced neonatal tolerance prevents autoimmunity by an organ-specific regulation of T cells that involves both immune deviation and a new form of cytokine- dependent T cell anergy.

scholarly journals Mapping of Murine Th1 Helper T-Cell Epitopes of Mycolyl Transferases Ag85A, Ag85B, and Ag85C from Mycobacterium tuberculosis

2003 ◽  
Vol 71 (1) ◽  
pp. 483-493 ◽  
Author(s):  
S. D'Souza ◽  
V. Rosseels ◽  
M. Romano ◽  
A. Tanghe ◽  
O. Denis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Mouse Strains ◽  
T Cell Epitopes ◽  
Dna Encoding ◽  
Amino Acid Region ◽  
Ifn Γ ◽  
Carboxy Terminal

ABSTRACT BALB/c (H-2d ) and C57BL/6 (H-2b ) mice were infected intravenously with Mycobacterium tuberculosis H37Rv or vaccinated intramuscularly with plasmid DNA encoding each of the three mycolyl transferases Ag85A, Ag85B, and Ag85C from M. tuberculosis. Th1-type spleen cell cytokine secretion of interleukin-2 (IL-2) and gamma interferon (IFN-γ) was analyzed in response to purified Ag85 components and synthetic overlapping peptides covering the three mature sequences. Tuberculosis-infected C57BL/6 mice reacted strongly to some peptides from Ag85A and Ag85B but not from Ag85C, whereas tuberculosis-infected BALB/c mice reacted only to peptides from Ag85A. In contrast, spleen cells from both mouse strains produced elevated levels of IL-2 and IFN-γ following vaccination with Ag85A, Ag85B, and Ag85C DNA in response to peptides of the three Ag85 proteins, and the epitope repertoire was broader than in infected mice. Despite pronounced sequence homology, a number of immunodominant regions contained component specific epitopes. Thus, BALB/c mice vaccinated with all three Ag85 genes reacted against the same amino acid region, 101 to 120, that was also immunodominant for Ag85A in M. bovis BCG-vaccinated and tuberculosis-infected H-2d haplotype mice, but responses were completely component specific. In C57BL/6 mice, a cross-reactive T-cell response was detected against two carboxy-terminal peptides spanning amino acids 241 to 260 and 261 to 280 of Ag85A and Ag85B. These regions were not recognized at all in C57BL/6 mice vaccinated with Ag85C DNA. Our results underline the need for comparative analysis of all three Ag85 components in future vaccination studies.

scholarly journals Cryptosporidium parvum-Specific CD4 Th1 Cells from Sensitized Donors Responding to Both Fractionated and Recombinant Antigenic Proteins

2004 ◽  
Vol 72 (3) ◽  
pp. 1306-1310 ◽  
Author(s):  
Maria Angeles Gomez Morales ◽  
Raffaella Mele ◽  
Alessandra Ludovisi ◽  
Fabrizio Bruschi ◽  
Fabio Tosini ◽  
...  
Keyword(s):  
T Cell ◽  
Cryptosporidium Parvum ◽  
Cellular Response ◽  
Mononuclear Cells ◽  
Early Stage ◽  
T Cell Response ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
Human T Cell ◽  
Ifn Γ

ABSTRACT T-cell-mediated immunity plays a central role in the host response to Cryptosporidium parvum. Human T-cell clones (TCC) were isolated from peripheral blood mononuclear cells of five healthy donors with prior cryptosporidiosis by use of a C. parvum crude extract, two antigen fractions obtained by ion-exchange chromatography (IEC1 and IEC2), and two recombinant peptides (SA35 and SA40) from C. parvum sporozoites. The T-cell lines derived from the one recently infected donor had a higher proportion (26 to 38%) of T cells exhibiting the γ/δ T-cell receptor (γ/δ-TCR) than those from donors who had recovered from cryptosporidiosis several years earlier, suggesting that the γ/δ T-cell population is involved in the early stage of the infection. The specific TCC had the α/β-TCR, had the phenotype CD45RO+ CD4+ CD8−, and were characterized by either hyperproduction of gamma interferon (IFN-γ) alone, with a Th1 profile, or IFN-γ hyperproduction together with interleukin-4 (IL-4) or IL-5 production, with a Th0 profile. SA35, SA40, IEC1, and IEC2 may be considered good targets of the cellular response against C. parvum and may play a role in maintaining the T-cell-mediated memory response to this parasite. Furthermore, the SA35 and SA40 peptides may be regarded as immunodominant antigens involved in the maintenance of the T-cell response in healthy C. parvum-sensitized persons.

scholarly journals Priming of a β-Galactosidase (β-GAL)-Specific Type 1 Response in BALB/c Mice Infected with β-GAL-Transfected Leishmania major

2000 ◽  
Vol 68 (2) ◽  
pp. 809-814 ◽  
Author(s):  
Hrishekesh R. Chakkalath ◽  
Afzal A. Siddiqui ◽  
Anuraj H. Shankar ◽  
Deborah E. Dobson ◽  
Stephen M. Beverley ◽  
...  
Keyword(s):  
T Cell ◽  
Leishmania Major ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Interleukin 4 ◽  
Th2 Response ◽  
C3h Mice ◽  
Ifn Γ ◽  
T Cell Lines

ABSTRACT To determine whether an ongoing response to Leishmania major would affect the response to a non-cross-reacting, non-leishmanial antigen, susceptible BALB/c mice and resistant C3H mice were infected with L. major parasites expressingEscherichia coli β-galactosidase (β-GAL); this parasite was designated L. major-βGAL. BALB/c and C3H mice responded to infection with L. major-βGAL by mounting a CD4 T-cell response to both parasite antigens and to the reporter antigen, β-GAL. The phenotypes of these T cells were characterized after generating T-cell lines from infected mice. As expected, BALB/c mice responded to infection with L. major-βGAL by producing interleukin 4 in response to the parasite and C3H mice produced gamma interferon (IFN-γ) in response to the parasite and β-GAL. Interestingly, however, BALB/c mice produced IFN-γ in response to β-GAL. Taken together, these results demonstrate that priming of IFN-γ-producing cells can occur in BALB/c mice despite the fact the animals are simultaneously mounting a potent Th2 response toL. major.

scholarly journals B- and T-Cell Immune Responses to Pneumococcal Conjugate Vaccines: Divergence between Carrier- and Polysaccharide-Specific Immunogenicity

1999 ◽  
Vol 67 (9) ◽  
pp. 4862-4869 ◽  
Author(s):  
Tera L. McCool ◽  
Clifford V. Harding ◽  
Neil S. Greenspan ◽  
John R. Schreiber
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Antibody Response ◽  
Antigen Processing ◽  
T Cell Responses ◽  
T Cell Response ◽  
Carrier Protein ◽  
Reactive Material ◽  
Cell Responses ◽  
Lymph Node Cells

ABSTRACT Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material197 (CRM197) produce a strong anti-PnPS antibody response; however, when mice are immunized with 23F PnPS conjugated to CRM197, they fail to produce a significant anti-PnPS response. In order to determine whether this difference was related to alterations in antigen processing of the carrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM197 alone or conjugated to 6B, 19F, or 23F PnPS. T-cell proliferative responses to synthetic peptides demonstrated that lymph node cells elicited by the poorly immunogenic conjugate 23F-CRM197 recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM197 as well as additional epitopes. Despite marked differences in PnPS-specific immunogenicity, all mice made high titers of CRM197 antibodies of the immunoglobulin G1 isotype. Cells from mice immunized with any of the conjugates yielded vigorous T-cell responses to whole antigen. We conclude that the serotype of PnPS can alter the peptide specificities of T-cell responses, but even a poorly immunogenic PnPS conjugate can elicit a significant T-cell response. Thus, conjugation of PnPS to a carrier protein that elicits carrier-specific T- and B-cell responses does not necessarily enhance PnPS immunogenicity.

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