scholarly journals B2 but Not B1 Cells Can Contribute to CD4+ T-Cell-Mediated Clearance of Rotavirus in SCID Mice

2001 ◽  
Vol 75 (12) ◽  
pp. 5482-5490 ◽  
Author(s):  
Natasha Kushnir ◽  
Nicolaas A. Bos ◽  
Adrian W. Zuercher ◽  
Susan E. Coffin ◽  
Charlotte A. Moser ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Secondary Infection ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Scid Mice ◽  
Peritoneal Exudate ◽  
Peritoneal Exudate Cells ◽  
B1 Cells ◽  
Intestinal Iga

ABSTRACT Studies utilizing various immunodeficient mouse models of rotavirus (RV) infection demonstrated significant roles of RV-specific secretory immunoglobulin A (IgA), CD4+ T cells, and CD8+T cells in the clearance of RV and protection from secondary infection. Secretion of small but detectable amounts of IgA in RV-infected αβ T-cell receptor knockout mice (11) and distinctive anatomical localization and physiology of B1 cells suggested that B1 cells might be capable of producing RV-specific intestinal IgA in a T-cell-independent fashion and, therefore, be responsible for ablation of RV shedding. We investigated the role of B1 cells in the resolution of primary RV infection using a SCID mouse model. We found that the adoptive transfer of unseparated peritoneal exudate cells ablates RV shedding and leads to the production of high levels of RV-specific intestinal IgA. In contrast, purified B1 cells do not ablate RV shedding and do not induce a T-cell-independent or T-cell-dependent, RV-specific IgA response but do secrete large amounts of polyclonal (total) intestinal IgA. Cotransfer of mixtures of purified B1 cells and B1-cell-depleted peritoneal exudate cells differing in IgA allotypic markers also demonstrated that B2 cells (B1-cell-depleted peritoneal exudate cells) and not B1 cells produced RV-specific IgA. To our knowledge, this is the first observation that B1 cells are unable to cooperate with CD4+ T cells and produce virus-specific intestinal IgA antibody. We also observed that transferred CD4+ T cells alone are capable of resolving RV shedding, although no IgA is secreted. These data suggest that RV-specific IgA may not be obligatory for RV clearance but may protect from reinfection and that effector CD4+ T cells alone can mediate the resolution of primary RV infection. Reconstitution of RV-infected SCID mice with B1 cells results in the outgrowth of contaminating, donor CD4+ T cells that are unable to clear RV, possibly because their oligoclonal specificities may be ineffective against RV antigens.

scholarly journals Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation.

1993 ◽  
Vol 177 (1) ◽  
pp. 191-194 ◽  
Author(s):  
D E Mosier ◽  
K L Stell ◽  
R J Gulizia ◽  
B E Torbett ◽  
G L Gilmore
Keyword(s):  
T Cells ◽  
T Cell ◽  
Receptor Gene ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Scid Mice ◽  
Immunoglobulin Production ◽  
T Cell Receptor Gene ◽  
Low Levels ◽  
Or Genes

The autosomal recessive scid mutation results in defective immunoglobulin and T cell receptor gene rearrangement. The scid mutation occurred in the allotype congenic C.B-17 line, and up to 25% of C.B-17 scid mice spontaneously produce both T cells and immunoglobulin, a phenotype known as "leaky." Moreover, introduction of neonatal T cells into C.B-17 scid mice leads to immunoglobulin production by 100% of animals. We have produced mice homozygous for both the scid and beige mutations. By contrast with C.B-17 scid mice, BALB/c scid.beige mice have a < 2% incidence of "leakiness." This percentage does not increase with age, and introduction of neonatal T cells fails to rescue immunoglobulin production. This suggests that a gene (or genes) closely linked to the beige locus regulates B and/or T cell development.

scholarly journals T cell-independent antibody-mediated clearance of polyoma virus in T cell-deficient mice.

1996 ◽  
Vol 183 (2) ◽  
pp. 403-411 ◽  
Author(s):  
E Szomolanyi-Tsuda ◽  
R M Welsh
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Nude Mice ◽  
Knockout Mice ◽  
Cell Receptor ◽  
Genetically Engineered ◽  
Scid Mice ◽  
Myeloproliferative Disease ◽  
Alpha Beta

Polyomavirus (PyV) infection of SCID mice, which lack functional T and B cells, leads to a lethal acute myeloproliferative disease (AMD) and to high levels of virus replication in several organs by two wk after infection. This is in contrast to infection of T cell-deficient athymic nude mice, which are resistant to acute PyV-induced disease and poorly replicate the virus in their organs. This major difference in the virus load and in the outcome of PyV infection between SCID and nude mice suggested that an efficient, T cell-independent antiviral mechanism operates in T cell-deficient, PyV infected mice. To investigate this possibility, mice with different genetically engineered T and/or B cell deficiencies and SCID mice adoptively reconstituted with B and/or T cells were infected with PyV. The results indicated that the presence of B cells in the absence of T cells protected mice from the AMD, and this was accompanied by a major reduction of PyV in all organs tested. Sera from PyV-infected T cell receptor (TCR) alpha beta knockout or TCR alpha beta gamma delta knockout mice contained IgG2a antibodies to PyV. Sera or purified immunoglobulin fractions from PyV-infected TCR alpha beta knockout mice protected SCID mice from the PyV-induced AMD. To our knowledge, this is the first report of an effective T cell-independent antibody response clearing a virus and changing the outcome of infection from 100% mortality to 100% survival.

scholarly journals Eradication of Cryptosporidium parvumInfection by Mice with Ovalbumin-Specific T Cells

2000 ◽  
Vol 68 (5) ◽  
pp. 2663-2670 ◽  
Author(s):  
Kara Lukin ◽  
Mary Cosyns ◽  
Tom Mitchell ◽  
Milton Saffry ◽  
Anthony Hayward
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cryptosporidium Parvum ◽  
Dna Sequences ◽  
Cell Receptor ◽  
Scid Mice ◽  
Fecal Excretion ◽  
Cell Effector

ABSTRACT CD154 is necessary for mice to clear a Cryptosporidium parvum infection, but whether this ligand has to be expressed on T cells with specificity for C. parvum has not been determined. We infected DO11.10 (ovalbumin specific) T-cell receptor transgenic mice that had been bred to a RAG−/− background with C. parvum and found that the infection was cleared within 6 weeks, while RAG−/− controls were unable to clear C. parvum infection. Recovery was accompanied by an increase in the number of splenic T cells with the CD44highphenotype that characterizes memory cells. To determine whether aC. parvum-infected environment sufficed to activate transgenic T cells, we reconstituted C. parvum-infected BALB/c SCID mice with DO11.10 RAG−/− splenocytes. Fecal excretion of C. parvum antigen ceased in the 12 weeks following the adoptive transfer, unless the mice were also injected with tolerizing doses of ovalbumin. DO11.10 T cells were found in the submucosa of C. parvum-infected, but not uninfected, BALB/c SCID hosts within 48 h of injection. The transferred DO11.10 T cells divided and acquired a CD44high memory phenotype inC. parvum-infected, but not uninfected, recipients. DO11.10 splenocytes from CD154 knockout donors failed to clear a C. parvum infection, confirming a requirement for CD154 in recovery. In vitro, the DO11.10 cells did not proliferate in response to C. parvum antigen, and a tBlast GenBank search revealed no matches between the ovalbumin peptide and C. parvum DNA sequences.C. parvum-infected SCID mice given RAG−/−CD8+ T cells with a Listeria-specific transgene did not recover from C. parvum infection. Our data suggest that antigen-nonspecific CD4+ T-cell effector mechanisms in combination with the innate arm of the immune system are sufficient for the eradication of C. parvum infection.

scholarly journals The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system.

1993 ◽  
Vol 177 (3) ◽  
pp. 821-832 ◽  
Author(s):  
T R Kollmann ◽  
M M Goldstein ◽  
H Goldstein
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Keyhole Limpet Hemocyanin ◽  
Cell Receptor ◽  
Scid Mice ◽  
Double Positive ◽  
Fetal Thymus

To determine whether the human thymus provides an environment for the maturation of murine T cells, human fetal thymus and liver (hu-thy/liv) were implanted into congenitally athymic NIH-beige-nude-xid (BNX) mice or C.B-17 scid/scid (SCID) mice. 3 mo after implantation, in contrast to the hu-thy/liv implant in SCID mice, which was populated only with human CD4/CD8 single- and double-positive thymocytes, the hu-thy/liv implant in BNX mice contained a chimeric population of human and mouse CD4/CD8 single- and double-positive thymocytes. Immunohistochemical staining of the hu-thy/liv implant in BNX mice indicated that the population of double-positive mouse thymocytes was localized to discrete areas of the human fetal thymus. Quantitative improvements in mouse T cell and immunoglobulin (Ig) G parameters were observed after grafting of the human fetal thymus and liver tissue into BNX mice. In addition, in contrast to the nonimplanted BNX mice, the implanted BNX mice were capable of mounting a keyhole limpet hemocyanin-specific IgG response and their peripheral T cells were responsive to stimulation with mitogens and antibodies directed to the T cell receptor. Furthermore, after in vivo priming, T cells present in lymph nodes of the implanted BNX mice were capable of mounting an antigen-induced in vitro T cell-dependent proliferative response. Thus, concurrent with the continued maturation of human T cells, murine T cells differentiated within the human fetal thymus implanted in the BNX mice and mediated the phenotypic and functional reconstitution of the murine immune system. Mice with a reconstituted immune system that contain a human thymic implant that is infectible with human immunodeficiency virus (HIV) should prove useful in the investigation of T cell maturation in the thymus and in the evaluation of potential HIV vaccines.

scholarly journals Adoptive transfer of neonatal T lymphocytes rescues immunoglobulin production in mice with severe combined immune deficiency.

1991 ◽  
Vol 173 (1) ◽  
pp. 265-268 ◽  
Author(s):  
J E Riggs ◽  
R S Stowers ◽  
D E Mosier
Keyword(s):  
Immune Deficiency ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Autosomal Recessive ◽  
Low Frequency ◽  
Cell Receptor ◽  
Scid Mice ◽  
Severe Combined Immune Deficiency ◽  
Combined Immune Deficiency

Mice with the autosomal recessive severe combined immune deficiency (scid) mutation lack mature lymphocytes because of defective joining of T cell receptor and immunoglobulin (Ig) gene segments. Penetrance of this mutation is incomplete since 10-25% of SCID mice produce some T or B lymphocytes. This "leaky" phenotype could be due to a reversion of the mutation in some mice or to a constant, low frequency of functional lymphocytes generated in all SCID mice with variable survival of such cells. We report here that all SCID mice can be stimulated to produce functional B cells by the transfer of normal neonatal, but not adult, T cells. T cell-induced rescue of C.B-17scid B cells results in high levels of Ig expressing the Ighb allotype of the SCID recipient. These results show that all SCID mice generate some functional B cells, the majority of which do not survive in the absence of a subset of T cells present in high frequency in the neonate.

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