scholarly journals A Deficiency in Gamma Interferon or Interleukin-10 Modulates T-Cell-Dependent Responses to Heat Shock Protein 60 from Histoplasma capsulatum

2005 ◽  
Vol 73 (4) ◽  
pp. 2129-2134 ◽  
Author(s):  
Mark Scheckelhoff ◽  
George S. Deepe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Receptor ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Heat Shock Protein 60 ◽  
Wild Type ◽  
Deficient Mice

ABSTRACT Immunization of mice with heat shock protein 60 from Histoplasma capsulatum or a polypeptide from the protein designated F3 confers protection. Vβ8.1/8.2+ T cells are critically important for the protective efficacy of this antigen. The production of interleukin-10 and gamma interferon following vaccination is essential for efficacy. In this study, we sought to determine whether the absence of either cytokine modified the repertoire of antigen-reactive T cells and whether it altered the functional properties of T cells. Mice lacking gamma interferon or interleukin-10 manifested a skewed repertoire compared to that of wild-type mice. The bias was most marked in gamma interferon-deficient mice and modestly altered in interleukin-10-deficient animals. The altered repertoire in gamma interferon-deficient mice could not be explained at the level of antigen presentation or by the absence of this population from mice. The proportion of T cells from interleukin-10-deficient mice manifesting a Th1 phenotype was greatly increased compared to that from wild-type animals. Transfer of splenocytes from gamma interferon- or interleukin-10-deficient mice immunized with heat shock protein 60 failed to confer protection in T-cell receptor α/β−/− mice. The transfer of T-cell clones that did not produce both cytokines failed to prolong survival in T-cell receptor α/β−/− mice, whereas the clones with the same features that were derived from wild-type mice did. These results indicate that the cytokine milieu influences the shape of the T-cell receptor repertoire and support the importance of gamma interferon and interleukin-10 in the efficacy of heat shock protein 60.

scholarly journals Cellular and Molecular Regulation of Vaccination with Heat Shock Protein 60 from Histoplasma capsulatum

2002 ◽  
Vol 70 (7) ◽  
pp. 3759-3767 ◽  
Author(s):  
George S. Deepe ◽  
Reta S. Gibbons
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Histoplasma Capsulatum ◽  
Regulatory Elements ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Yeast Cells ◽  
Heat Shock Protein 60 ◽  
Fungal Burden ◽  
Inductive Phase

ABSTRACT Vaccination with heat shock protein 60 (Hsp60) from Histoplasma capsulatum induces a protective immune response in mice. We explored the cellular and molecular requirements for the efficacy of recombinant Hsp60 in mice. Depletion of CD4+, but not CD8+, cells during the inductive phase of vaccination abolished protection, as assessed by survival and by the fungal burden in lungs and spleens. In the expressive phase, the elimination of CD4+ or CD8+ cells after immunization did not significantly alter fungal recovery or survival from a lethal challenge. Depletion of both subpopulations after Hsp60 vaccination resulted in a failure to control a lethal infection and a higher fungal burden in lungs and spleens. Cytokine release by spleen cells from mice vaccinated with Hsp60 produced substantially more gamma interferon and interleukin-10 and -12 than that of cells from mice immunized with either H. capsulatum recombinant Hsp70 or bovine serum albumin. The generation of gamma interferon, but not of interleukin-10, was dependent on T cells, in particular CD4+ cells. Treatment of Hsp60-immunized mice with monoclonal antibody to gamma interferon or interleukin-10 or -12 in the inductive phase of vaccination was accompanied by increased recovery of yeast cells from lungs and spleens and 100% mortality. Likewise, the neutralization of gamma interferon or interleukin-12 abolished the protective effect of Hsp60 in the expressive phase. These results delineate the complexity of the regulatory elements necessary for vaccination against this fungus.

scholarly journals T Cell-Independent Gamma Interferon and B Cells Cooperate To Prevent Mortality Associated with DisseminatedChlamydia muridarumGenital Tract Infection

2018 ◽  
Vol 86 (7) ◽  
pp. e00143-18 ◽  
Author(s):  
Taylor B. Poston ◽  
Catherine M. O'Connell ◽  
Jenna Girardi ◽  
Jeanne E. Sullivan ◽  
Uma M. Nagarajan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Tract Infection ◽  
B Cell ◽  
Gamma Interferon ◽  
Wild Type ◽  
Content Type ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACTCD4 T cells and antibody are required for optimal acquired immunity toChlamydia muridarumgenital tract infection, and T cell-mediated gamma interferon (IFN-γ) production is necessary to clear infection in the absence of humoral immunity. However, the role of T cell-independent immune responses during primary infection remains unclear. We investigated this question by inoculating wild-type and immune-deficient mice withC. muridarumCM001, a clonal isolate capable of enhanced extragenital replication. Genital inoculation of wild-type mice resulted in transient dissemination to the lungs and spleen that then was rapidly cleared from these organs. However, CM001 genital infection proved lethal forSTAT1−/−andIFNG−/−mice, in which IFN-γ signaling was absent, and forRag1−/−mice, which lacked T and B cells and in which innate IFN-γ signaling was retained. In contrast, B cell-deficient muMT mice, which can generate a Th1 response, and T cell-deficient mice with intact B cell and innate IFN-γ signaling survived. These data collectively indicate that IFN-γ prevents lethal CM001 dissemination in the absence of T cells and suggests a B cell corequirement. Adoptive transfer of convalescent-phase immune serum but not naive IgM toRag1−/−mice infected with CM001 significantly increased the survival time, while transfer of naive B cells completely rescuedRag1−/−mice from CM001 lethality. Protection was associated with a significant reduction in the lung chlamydial burden of genitally infected mice. These data reveal an important cooperation between T cell-independent B cell responses and innate IFN-γ in chlamydial host defense and suggest that interactions between T cell-independent antibody and IFN-γ are essential for limiting extragenital dissemination.

Comparison of expression of heat-shock protein 60, Toll-like receptors 2 and 4, and T-cell receptor γδ in plaque and guttate psoriasis

2007 ◽  
Vol 34 (12) ◽  
pp. 903-911 ◽  
Author(s):  
Na Reu Seung ◽  
Eun Joo Park ◽  
Chul Woo Kim ◽  
Kwang Ho Kim ◽  
Kwang Joong Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Heat Shock Protein 60 ◽  
Toll Like Receptors ◽  
Guttate Psoriasis

scholarly journals Resistance of T-Cell Receptor δ-Chain-Deficient Mice to Experimental Candidaalbicans Vaginitis

2001 ◽  
Vol 69 (11) ◽  
pp. 7162-7164 ◽  
Author(s):  
Floyd L. Wormley ◽  
Chad Steele ◽  
Karen Wozniak ◽  
Kohtaro Fujihashi ◽  
Jerry R. McGhee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Vaginal Candidiasis ◽  
Wild Type ◽  
Vaginal Infections ◽  
Deficient Mice ◽  
Δ Chain

ABSTRACT Conditions consistent with tolerance or immunoregulation have been observed in experimental Candida albicansvaginal infections. The present study investigated the role of γ/δ T cells in experimental vaginal candidiasis. Results showed that T-cell receptor δ-chain-knockout mice had significantly less vaginal fungal burden when compared to wild-type mice, suggesting an immunoregulatory role for γ/δ T cells in Candidavaginitis.

T-Cell Receptor Variable γ Chain Gene Expression in the Interaction between Rat γδ-Type T Cells and Heat-Shock Protein 70-Like Molecule

2003 ◽  
Vol 47 (5) ◽  
pp. 351-357 ◽  
Author(s):  
Takashi Ichinohe ◽  
Shingo Ichimiya ◽  
Akihiko Kishi ◽  
Yasuaki Tamura ◽  
Nobuhiko Kondo ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Receptor ◽  
Heat Shock Protein 70 ◽  
Cell Receptor ◽  
Chain Gene

scholarly journals Plasma Membrane Expression of Heat Shock Protein 60 In Vivo in Response to Infection

1999 ◽  
Vol 67 (8) ◽  
pp. 4191-4200 ◽  
Author(s):  
Cindy Belles ◽  
Alicia Kuhl ◽  
Rachel Nosheny ◽  
Simon R. Carding
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Receptor ◽  
T Cell Response ◽  
Heat Shock Protein 60 ◽  
Membrane Expression ◽  
Hsp60 Expression

ABSTRACT Heat shock protein 60 (hsp60) is constitutively expressed in the mitochondria of eukaryotic cells. However, it has been identified in other subcellular compartments in several disease states and in transformed cells, and it is an immunogenic molecule in various infectious and autoimmune diseases. To better understand the factors that influence expression of hsp60 in normal cells in vivo, we analyzed its cellular and subcellular distribution in mice infected with the intracellular bacterium Listeria monocytogenes. Western blotting of subcellular fractionated spleen cells showed that although endogenous hsp60 was restricted to the mitochondria in noninfected animals, it was associated with the plasma membrane as a result of infection. The low levels of plasma membrane-associated hsp60 seen in the livers in noninfected animals subsequently increased during infection. Plasma membrane hsp60 expression did not correlate with bacterial growth, being most evident during or after bacterial clearance and persisting at 3 weeks postinfection. Using flow cytometry, we determined that Mac-1+, T-cell receptor γδ+, and B220+ cells represented the major Hsp60+ populations in spleens of infected mice. By contrast, B220+ cells were the predominant hsp60+ population in livers of infected mice. Of the immune cells analyzed, the kinetic profile of the γδ T-cell response most closely matched that of hsp60 expression in both the spleen and liver. Collectively, these findings show that during infection hsp60 can be localized to the plasma membrane of viable cells, particularly antigen-presenting cells, providing a means by which hsp60-reactive lymphocytes seen in various infectious disease and autoimmune disorders may be generated and maintained.

scholarly journals T-Cell-Dependent Control of Acute Giardia lamblia Infections in Mice

2000 ◽  
Vol 68 (1) ◽  
pp. 170-175 ◽  
Author(s):  
Steven M. Singer ◽  
Theodore E. Nash
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Giardia Lamblia ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Wild Type ◽  
Adult Mice ◽  
Giardia Muris ◽  
Deficient Mice

ABSTRACTWe have studied immune mechanisms responsible for control of acuteGiardia lambliaandGiardia murisinfections in adult mice. Association of chronicG. lambliainfection with hypogammaglobulinemia and experimental infections of mice withG. murishave led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with eitherG. lambliaorG. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection withG. lamblia. G. muriswas also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient andscidmice failed to controlG. lambliainfections, as has been shown previously forG. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination ofG. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either αβ- or γδ-T-cell receptor (TCR)-expressing T cells, we show that the αβ-TCR-expressing T cells are required to control parasites but that the γδ-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection fromG. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acuteGiardiainfections and that this mechanism is independent of antibody and B cells.

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