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.

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.

scholarly journals Critical Role of T Cells in PF4/Heparin Antibody Production

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1554-1554
Author(s):  
Yongwei Zheng ◽  
Mei Yu ◽  
Anand Padmanabhan ◽  
Richard H. Aster ◽  
Renren Wen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antibody Production ◽  
Cd4 T Cells ◽  
Wild Type ◽  
Specific Antibodies ◽  
Deficient Mice

Abstract Heparin-induced thrombocytopenia (HIT) is an antibody-mediated disorder that can cause arterial or venous thrombosis/thromboembolism, and platelet factor 4 (PF4)/ heparin-reactive antibodies are essential to the pathogenesis of HIT. Our recent studies have demonstrated that marginal zone (MZ) B cells play a major role in production of PF4/heparin-specific antibodies. However, the role of T cells in production of these pathogenic antibodies is not clear. Here we showed that PF4/heparin complex-induced production of PF4/heparin-specific antibodies was markedly impaired in mice, in which CD4 T cells were depleted by administration of GK1.5 anti-CD4 monoclonal antibody. As expected, the CD4 T cell-depleted mice responded normally to T cell-independent antigen TNP-Ficoll but not T cell-dependent antigen NP-CGG, in agreement with the lack of CD4 T cells in these GK1.5-treated mice. Further, following adoptive transfer of a mixture of wild-type splenic B cells and splenocytes from B cell-deficient μMT mice, T and B cell-deficient Rag1 knockout mice responded to PF4/heparin complex challenge to produce PF4/heparin-specific antibodies. In contrast, Rag1-deficient mice that received a mixture of wild-type splenic B cells and splenocytes from Rag1-deficient mice barely produced PF4/heparin-specific antibodies upon PF4/heparin complex challenge. These data suggest that T cells are required for production of PF4/heparin-specific antibodies. Consistent with this concept, mice with B cells lacking CD40 molecule, a B cell costimulatory molecule that helps T cell-dependent B cell responses, displayed a marked reduction of PF4/heparin-specific antibody production following PF4/heparin complex challenge. Also as expected, mice with CD40-deficient B cells were able to respond to T cell-independent antigen TNP-Ficoll but not T cell-dependent antigen NP-CGG, consistent with the lack of T-cell help in these mice. Taken together, these findings demonstrate that T cells play an essential role in production of PF4/heparin-specific antibodies by MZ B cells. Disclosures No relevant conflicts of interest to declare.

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 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.

scholarly journals B cells are essential for murine mammary tumor virus transmission, but not for presentation of endogenous superantigens.

1994 ◽  
Vol 179 (5) ◽  
pp. 1457-1466 ◽  
Author(s):  
U Beutner ◽  
E Kraus ◽  
D Kitamura ◽  
K Rajewsky ◽  
B T Huber
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Mammary Tumor ◽  
Cell Receptor ◽  
Mammary Tissue ◽  
Murine Mammary Tumor ◽  
Deficient Mice

Murine mammary tumor viruses (MMTVs) are retroviruses that encode superantigens capable of stimulating T cells via superantigen-reactive T cell receptor V beta chains. MMTVs are transmitted to the suckling offspring through milk. Here we show that B cell-deficient mice foster nursed by virus-secreting mice do not transfer infectious MMTVs to their offspring. No MMTV proviruses could be detected in the spleen and mammary tissue of these mice, and no deletion of MMTV superantigen-reactive T cells occurred. By contrast, T cell deletion and positive selection due to endogenous MMTV superantigens occurred in B cell-deficient mice. We conclude that B cells are essential for the completion of the viral life cycle in vivo, but that endogenous MMTV superantigens can be presented by cell types other than B cells.

scholarly journals Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1286-1295 ◽  
Author(s):  
Yoshihiko Tanaka ◽  
Takanori So ◽  
Svetlana Lebedeva ◽  
Michael Croft ◽  
Amnon Altman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Th1 Cell ◽  
Activated T Cell ◽  
Ifn Γ ◽  
Th2 Differentiation ◽  
Deficient Mice

AbstractAlthough c-Maf is crucial for Th2 differentiation and production of interleukin 4 (IL-4), its regulation is poorly understood. We report that Vav1–/– CD4+ T cells display deficient T-cell receptor (TCR)/CD28-induced IL-4 and c-Maf expression and, conversely, enhanced interferon γ (IFN-γ) production and T-bet expression (even when cultured under Th2-polarizing conditions), but intact expression of other Th2 cytokines and GATA-3. Up-regulation of c-Maf was dependent on Ca2+/nuclear factor of activated T cell (NFAT) and, together with IL-4 production, could be rescued in Vav1–/– T cells by Ca2+ ionophore. Deficient IL-4 production was restored by retrovirus-mediated Vav1 expression, but only partially by retroviral c-Maf expression. Similar IL-4 → IFN-γ skewing was observed in intact, antigen-primed Vav1–/– mice. Thus, Vav1 is selectively required for IL-4 and c-Maf expression, a requirement reflecting, at least in part, the dependence of c-Maf expression on Ca2+/NFAT signaling.

scholarly journals Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

1999 ◽  
Vol 190 (5) ◽  
pp. 607-616 ◽  
Author(s):  
Hideki Iijima ◽  
Ichiro Takahashi ◽  
Daisuke Kishi ◽  
Jin-Kyung Kim ◽  
Sunao Kawano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Bowel Disease ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
T Helper ◽  
Inflammatory Bowel ◽  
Α Chain

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4+TCR-ββ (CD4+ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4+ββ T cells, we treated TCR-α−/− mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-α−/− mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-α−/− mice treated with either specific or mock Ab developed CD4+ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon γ–specific expression. These findings suggest that IL-4–producing Th2-type CD4+ββ T cells play a major immunopathological role in the induction of IBD in TCR-α−/− mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4+ββ T cells to shift to the Th1 type.

scholarly journals A role for CD9 molecules in T cell activation.

1996 ◽  
Vol 184 (2) ◽  
pp. 753-758 ◽  
Author(s):  
X G Tai ◽  
Y Yashiro ◽  
R Abe ◽  
K Toyooka ◽  
C R Wood ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Cloning ◽  
Wild Type ◽  
Almost All ◽  
Antigen Presenting ◽  
Deficient Mice

Costimulation mediated by the CD28 molecule plays an important role in optimal activation of T cells. However, CD28-deficient mice can mount effective T cell-dependent immune responses, suggesting the existence of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) that can costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expressed on almost all mature T cells and to be a protein of approximately 24 kD molecular mass. By expression cloning, this molecule was identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was induced by independent ligation of CD3 and CD9, suggesting that colocalization of these two molecules is not required for T cell activation. The costimulation by anti-CD9 was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-type mice. Thus, these results indicate that CD9 serves as a molecule on T cells that can deliver a potent CD28-independent costimulatory signal.

Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor

1994 ◽  
Vol 14 (2) ◽  
pp. 1095-1103
Author(s):  
A L Burkhardt ◽  
T Costa ◽  
Z Misulovin ◽  
B Stealy ◽  
J B Bolen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Antigen Receptors ◽  
Cell Antigen

Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T-cell receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have studied signal transduction by chimeric immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin-2 secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.

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