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 Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

1992 ◽  
Vol 176 (2) ◽  
pp. 581-586 ◽  
Author(s):  
A A Izzo ◽  
R J North
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nude Mice ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Scid Mice ◽  
Bacillus Calmette Guerin ◽  
Mechanism Of Resistance ◽  
Independent Mechanism ◽  
Alpha Beta

Depleting thymectomized mice of CD4+ T cells, or CD4+ plus CD8+ T cells, rendered them incapable of resolving Bacillus-Calmette-Guerin (BCG) infection in their lives, spleens, kidneys, and lungs. However, it did not render them incapable of stabilizing infection in the latter three organs after an initial period of BCG growth. Athymic nude mice showed a similar capacity to control BCG growth in these organs after a certain stage of infection. In contrast, congenitally severe combined immunodeficient (SCID) mice appeared to offer no resistance to BCG infection, in that the organism grew progressively in all organs of these mice and was lethal for them beginning on day 55 of infection. The results suggest that, although CD4+ T cells are important for resolving BCG infection, an alpha/beta T cell-independent mechanism of resistance can be acquired at 2-3 wk of infection that is capable of inhibiting further BCG growth in all organs except the lungs. Because this mechanism is absent from SCID mice, it is likely that it depends on the functions of gamma/delta T cells, B cells, or both types of cells. In keeping with this possibility is the additional finding that SCID mice engrafted with lymph node cells depleted of CD4+ or CD8+ T cells were capable of expressing an appreciable level of resistance against BCG infection.

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.

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells

scholarly journals Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats.

1992 ◽  
Vol 175 (4) ◽  
pp. 907-915 ◽  
Author(s):  
S Yoshino ◽  
L G Cleland
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Adjuvant Arthritis ◽  
Inflammatory Cells ◽  
Cell Receptor ◽  
Collagen Induced Arthritis ◽  
Alpha Beta ◽  
Synovial Tissues

The effects of treatment with a monoclonal antibody (R73 mAb) against T cell receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA) and established collagen-induced arthritis (ECIA) in rats have been investigated. Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and minimal erosion of cartilage, whereas arthritic rats treated with PBS and an irrelevant control mAb against Giardia had marked hyperplasia of synovium with pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced formation of pannus containing many inflammatory cells and marked cartilage and subchondral damage similar to those in arthritic rats that received the control treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb treatment was associated with marked reduction in arthritogen-specific delayed-type hypersensitivity responses in both EAA and ECIA. The titers of antibodies against type II collagen produced in rats with ECIA were not affected by the mAb. Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in chronic ECIA.

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 The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria.

1991 ◽  
Vol 174 (2) ◽  
pp. 417-424 ◽  
Author(s):  
T Abo ◽  
T Ohteki ◽  
S Seki ◽  
N Koyamada ◽  
Y Yoshikai ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Double Positive ◽  
Systematic Analysis ◽  
Cell Clones ◽  
Bacterial Stimulation ◽  
Alpha Beta ◽  
Peak Pattern

We demonstrated in the present study that with bacterial stimulation, an increased number of alpha/beta T cells proliferated in the liver of mice and that even T cells bearing self-reactive T cell receptor (TCR) (or forbidden T cell clones), as estimated by anti-V beta monoclonal antibodies in conjunction with immunofluorescence tests, appeared in the liver and, to some extent, in the periphery. The majority (greater than 80%) of forbidden clones induced had double-negative CD4-8-phenotype. In a syngeneic mixed lymphocyte reaction, these T cells appear to be self-reactive. Such forbidden clones and normal T cells in the liver showed a two-peak pattern of TCR expression, which consisted of alpha/beta TCR dull and bright positive cells, as seen in the thymus. A systematic analysis of TCR staining patterns in the various organs was then carried out. T cells from not only the thymus but also the liver had the two-peak pattern of alpha/beta TCR, whereas all of the other peripheral lymphoid organs had a single-peak pattern of TCR. However, T cells in the liver were not comprised of double-positive CD4+8+ cells, which predominantly reside in the thymus. The present results therefore suggest that T cell proliferation in the liver might reflect a major extrathymic pathway for T cell differentiation and that this hepatic pathway has the ability to produce T cells bearing self-reactive TCR under bacterial stimulation, probably due to the lack of a double-positive stage for negative selection.

scholarly journals Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

1996 ◽  
Vol 183 (5) ◽  
pp. 2271-2282 ◽  
Author(s):  
L Wen ◽  
W Pao ◽  
F S Wong ◽  
Q Peng ◽  
J Craft ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Autoantibody Production ◽  
Ige Synthesis ◽  
Alpha Beta ◽  
T Cell Help

The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.

scholarly journals A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

1995 ◽  
Vol 15 (12) ◽  
pp. 7022-7031 ◽  
Author(s):  
J Shutter ◽  
J A Cain ◽  
S Ledbetter ◽  
M D Rogers ◽  
R D Hockett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gamma Delta ◽  
Alpha Chain ◽  
Chain Locus ◽  
Discrete Population ◽  
Alpha Beta ◽  
Gamma Delta T Cell

T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.

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