scholarly journals B-Cell Deficiency Predisposes Mice to Disseminating Anaerobic Infections: Protection by Passive Antibody Transfer

2000 ◽  
Vol 68 (10) ◽  
pp. 5645-5651 ◽  
Author(s):  
Linda Hou ◽  
Hajime Sasakj ◽  
Philip Stashenko
Keyword(s):  
T Cell ◽  
B Cell ◽  
Adaptive Immune Response ◽  
Fusobacterium Nucleatum ◽  
Significant Loss ◽  
Genetically Engineered ◽  
Immunodeficient Mice ◽  
Systemic Spread ◽  
Anaerobic Infections ◽  
Deficient Mice

ABSTRACT We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not. In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis. For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc0 (C5 deficient). For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0. Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius,Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity. The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or C5-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections. Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production. Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IgM, against the infecting bacterial innoculum. Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations. We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread.

scholarly journals Inhibition of B-cell death does not restore T-cell-dependent immune responses in CD40-deficient mice

Immunology ◽  
2003 ◽  
Vol 109 (4) ◽  
pp. 504-509
Author(s):  
Jesus Merino ◽  
Miguel A. Diez ◽  
Maria Muniz ◽  
Luis Buelta ◽  
Gabriel Nunez ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Deficient Mice

scholarly journals Persistence and Tissue Distribution of DNA in Normal and Immunodeficient Mice Inoculated with Polyomavirus VP1 Pseudocapsid Complexes or Polyomavirus

2000 ◽  
Vol 74 (24) ◽  
pp. 11963-11965 ◽  
Author(s):  
S. Heidari ◽  
N. Krauzewicz ◽  
M. Kalantari ◽  
A. Vlastos ◽  
B. E. Griffin ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Infection ◽  
Tissue Distribution ◽  
Natural Infection ◽  
Dna Transfer ◽  
Immunodeficient Mice ◽  
Deficient Mice

ABSTRACT Introduction of DNA into normal and immunodeficient mice, alone or in complex with VP1 pseudocapsids, has been compared to DNA transfer by viral infection. Similar to natural infection and in contrast to plasmid alone, VP1 pseudocapsids efficiently introduced DNA, which remained for months in normal mice and possibly longer in B- and T-cell-deficient mice.

scholarly journals T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cell Accumulation ◽  
Antigen Presenting ◽  
Deficient Mice

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

B cell deficient mice reject B16 melanoma via T cell mediated immunity that is not associated with autoimmunity

2000 ◽  
Vol 191 (4) ◽  
pp. S17-S18
Author(s):  
Jason S Gold ◽  
William G Hawkins ◽  
Ruben Dyall ◽  
Nathalie E Blachere ◽  
Alan N Houghton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
B16 Melanoma ◽  
Cell Mediated Immunity ◽  
Deficient Mice

From T-cell Engineering to CAR therapy: Progress and Prospects

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-23-SCI-23 ◽  
Author(s):  
Michel Sadelain
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Second Generation ◽  
Human Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Stress Test ◽  
Lymphocytic Leukemia ◽  
Immunodeficient Mice ◽  
Recombinant Receptors

The genetic engineering of T cells provides a means to rapidly generate anti-tumor T cells for any cancer patient. This approach is predicated on gene transfer technology that enables the expression of receptors for antigen and other gene products in primary T cells. Tumor targeting may be achieved through the transfer of a physiological receptor for antigen, which is known as the T cell receptor (TCR), or synthetic fusion receptors, which we grouped under the general term of chimeric antigen receptor (CAR). CARs are recombinant receptors for antigen, which, in a single molecule, redirect T cell specificity and eventually enhance anti-tumor potency. Functional augmentation is achieved through the design of second generation CARs, which not only redirect cytotoxicity, but also reprogram T cell function and longevity through their costimulatory properties. The combined activating and costimulatory domains incorporated in second-generation CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19 CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Two decades ago, we selected CD19 as the prime target for developing our CAR technology and provided the first proof-of-principle that CD19-targeted human peripheral blood T cells could eradicate a broad range of B cell malignancies in immunodeficient mice (Brentjens RJ, Riviere I, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. 2003;9(3):279-86). CD19 has since become the poster child for CAR therapies. Complete remissions have been reported from several centers in patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia and, most dramatically, acute lymphoblastic leukemia. Two types of second generation CARs, utilizing either CD28 or 4-1BB as their costimulatory signaling components, have been used in ALL patients. Both have yielded dramatic outcomes, in adults as well as in children. Our data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, while 4-1BB-based CARs direct a gradual T cell accumulation that may eventually overcome lesser functional potency. These distinct kinetic features can be exploited to further develop CAR T cell therapies for a variety of cancers. We have now modeled CD19 CAR therapy for ALL in a "stress test", wherein we purposefully lower the infused T cell doses to challenge the CAR therapy. We have compared novel CAR designs intended to recruit both CD28 and 4-1BB signaling. These quantitative analyses reveal striking disparities that hinge on subtle variations in the structural design of CARs and co-expressed costimulatory molecules. Remarkably, we find that some of the most effective engineering strategies activate and sustain the recruitment of the IFNβ pathway through the induction of IRF7, while lowering the induction of exhaustion markers relative to second generation CARs activating either CD28 or 4-1BB alone. The field is thus poised to move beyond the CD28 vs 4-1BB debate, which will be rendered obsolete by the emergence of superior CAR designs that coopt the use of costimulatory ligands, cytokines and/or checkpoint blockade inhibitors. A new field of immunopharmacology is emerging. Disclosures Sadelain: Juno Therapeutics: Consultancy, Equity Ownership, Other: Co-Founder, stockholder, Patents & Royalties: Licensed patents on CARs.

scholarly journals Loss of T Cell and B Cell Quiescence Precedes the Onset of Microbial Flora-Dependent Wasting Disease and Intestinal Inflammation in Gimap5-Deficient Mice

2010 ◽  
Vol 184 (7) ◽  
pp. 3743-3754 ◽  
Author(s):  
Michael J. Barnes ◽  
Halil Aksoylar ◽  
Philippe Krebs ◽  
Tristan Bourdeau ◽  
Carrie N. Arnold ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Intestinal Inflammation ◽  
Microbial Flora ◽  
Wasting Disease ◽  
Cell Quiescence ◽  
Deficient Mice

Expansion of the γδ T cell subset in vivo during bloodstage malaria in B cell-deficient mice

1996 ◽  
Vol 60 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Henri C. van der Heyde ◽  
M. Merle Elloso ◽  
Wun-Ling Chang ◽  
Barbara J. Pepper ◽  
Joan Batchelder ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Subset ◽  
Γδ T Cell ◽  
T Cell Subset ◽  
Deficient Mice

scholarly journals Formalin-Inactivated Coxiella burnetii Phase I Vaccine-Induced Protection Depends on B Cells To Produce Protective IgM and IgG

2013 ◽  
Vol 81 (6) ◽  
pp. 2112-2122 ◽  
Author(s):  
Guoquan Zhang ◽  
Ying Peng ◽  
Laura Schoenlaub ◽  
Alexandra Elliott ◽  
William Mitchell ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Phase I ◽  
B Cell ◽  
Coxiella Burnetii ◽  
Critical Role ◽  
Partial Protection ◽  
Content Type ◽  
Deficient Mice

ABSTRACTTo further understand the mechanisms of formalin-inactivatedCoxiella burnetiiphase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4+T cell, or CD8+T cell deficiency in mice significantly affects the ability of PIV to confer protection against aC. burnetiiinfection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4+T cell- or CD8+T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4+T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4+T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibitC. burnetiiinfectionin vivo, but only IgM from PIV-vaccinated CD4+T cell-deficient mouse sera inhibitedC. burnetiiinfection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection againstC. burnetiiinfection.

scholarly journals Targeted Inactivation of the Tetraspanin CD37 Impairs T-Cell-Dependent B-Cell Response under Suboptimal Costimulatory Conditions

2000 ◽  
Vol 20 (15) ◽  
pp. 5363-5369 ◽  
Author(s):  
Klaus-Peter Knobeloch ◽  
Mark D. Wright ◽  
Adrian F. Ochsenbein ◽  
Oliver Liesenfeld ◽  
Jürgen Löhler ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Viral Infections ◽  
Cell Interactions ◽  
Antibody Responses ◽  
Cellular Activation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Targeted Inactivation ◽  
Deficient Mice

ABSTRACT CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell–B-cell interactions which manifests itself under suboptimal costimulatory conditions.

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