Immune depression of the SJL/J mouse, a radioresistant and immunologically atypical inbred strain (original) (raw)

As the inbred mouse strain SJL/J displays increased resistance to several pathogens and as its immune system shows multiple specificities, it is tempting to infer a causal link between these observations. The first question that comes to mind is whether adaptive immunity plays a role, and a way to answer this question is to see if the resistance phenotype persists when adaptive immunity is depressed. Although it has long been known that irradiation causes repression of leukopoiesis in mice, the technical data available in the literature are of no help in the case of strain SJL/J, because it displays exceptional radioresistance. Here we show that exposure of SJL/J to ∼9 Gy, an intensity corresponding to the lethal dose 50 for the species Mus musculus, leads to serious but reversible alteration of leukopoiesis. This conclusion stems from an examination of the effects, 1-11 days post-exposure, of whole-body gamma-ray irradiation on leukocyte populations in the thymus and peripheral blood of young adult females. Immunodepression was most severe 4 days post-exposure. As in other strains, leukocyte populations displayed differential radiosensitivity, B (CD19 + ) cells being most sensitive, T (CD4 + /CD8 + ) cells moderately sensitive, and natural killer (NK1.1 + ) cells most resistant. Surprisingly, however, the helper/inducer T lymphocytes proved more resistant than the cytotoxic/suppressor T lymphocytes, contrarily to what is observed in other strains. The procedure described will make it possible to refute or establish reliably the existence of causal links between SJL-specific phenotypic traits and immune aberrations and to elucidate further the respective roles of innate and acquired immunity in determining the resistance of this strain to an array of viral diseases.

Sign up for access to the world's latest research.

checkGet notified about relevant papers

checkSave papers to use in your research

checkJoin the discussion with peers

checkTrack your impact

Immunity to in mice I. Adoptive transfer of immunity to with immune spleen cells and the effect of irradiation on the protection of immune mice

Veterinary Immunology and Immunopathology, 1984

Immunity to Babesia in mice. I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice. Vet. Immunol. Immunopathol., 5: 343-357. Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide-controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with cyclophosphamide (300 mg/kg) five days before a lethal B.rodhaini inoculation resulted in over 50% survival. This protective effect of cyclophosphamide is explained by its inhibiting effect on suppressor T-cells. The protection against B.rodhaini challenge infection afforded to immune Balb/c mice was completely resistant to a sublethal irradiation of 400 tad. Since B-lymphocyte function in antibody production is suppressed by this dose, the role of antibodies in the effector phase of the immunity appears to be of minor if any importance. A considerable degree of protection was still preserved after irradiation of immune animals with 875 rad. Sensitivity to this irradiation dose of all immunocompetent cells except macrophages and a small fraction of T-lymphocytes indicates the involvement of these cell types in the effector phase of the specific immunity. Highly radioresistant macrophages are therefore considered to play the major role but T-lymphocytes are also required for complete protection. INTRODUCTION Successful attempts have been made to convey protection against Babesia to susceptible animals by transfer of spleen cells of immune donor animals. By this method naive rats could be protected against B.rodhaini (Roberts, 1968) and mice against B.microti

Radiation sensitivity of T-lymphocytes from immunodeficient “wasted” mice

Cellular Immunology, 1990

Mice with the autosomal recessive gene "wasted" (wstlwst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of y-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated a similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thy1 + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thy I+ cells were observed. Furthermore, when cells were treated with y-rays in combination with Con A, Thy I + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies. o 1990 Academic press, Inc.

Resistance toInfections inMicewithDefects intheActivities ofMononuclear Phagocytes andNatural Killer Cells: Effects ofImmunomodulators inBeigeMiceand89Sr-Treated Mice

1982

Beige mice, which are a homolog of the Chediak-Higashi syndrome, and mice treated with 89Sr to destroy the bone marrow provide animal models of defects in mononuclear phagocyte and natural killer cell functions. The innate resistance of these mice to viruses such as herpes simplex and encephalomyocarditis viruses, however, is normal. Moreover, treatment of the mice with immunomodulators such as Propionibacterium acnes (formerly designated Corynebacterium parvum) and pyran produced a significant increase in resistance to encephalomyocarditis virus. The antiviral effect of P. acnes in 89Sr-treated mice was exhibited during marked monocytopenia and without evidence for an inflammatory influx of macrophages into the peritoneal cavity. Treatment with P. acnes was also effective in increasing the resistance of beige mice to infection with Listeria monocytogenes. Thus, immunomodulators can be effective in mice that exhibit impaired macrophage and natural killer cell functions.

A new locus for resistance to γ-radiation-induced thymic lymphoma identified using inter-specific consomic and inter-specific recombinant congenic strains of mice

Oncogene, 2002

Mice of the C57BL/6J inbred strain develop thymic lymphomas at very high frequency after acute girradiation, while mice of several inbred strains derived from the wild progenitor of the Mus spretus species and their F1 hybrids with C57BL/6J appear extremely resistant. Analysis of the genetic determinism of the gradiation-induced thymic lymphoma (RITL) resistance with the help of inter-specific consomic strains (ICS), which carry a single introgressed Mus spretus chromosome on a C57BL/6J genetic background, provide significant evidence for the existence of a thymic lymphoma resistance (Tlyr1) locus on chromosome 19. The subsequent analysis of the backcross progeny resulting from a cross between consomic mice heterozygous for the Mus spretus chromosome 19 and C57BL/ 6J mice, together with the study of inter-specific recombinant congenic strains (IRCS), suggest that this Tlyr1 locus maps within the D19Mit60 -D19Mit40 chromosome interval. In addition to the discovery of a new locus controlling RITL development, our study emphasizes the value of ICS and IRCS for the genetic analysis of cancer predisposition.

Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? 1. Challenge with ionizing radiation

Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 1995

In the present paper, we report data on the possible adaptive response, induced in vivo by exposure to ionizing radiation to a challenge treatment with the radiomimetic glycopeptide bleomycin (BLM). Lymphocytes from children living in Pripjat at the time of the Chernobyl accident, and thus hit by the initial acute dose of ionizing radiation, were treated for the last 5 h of culture with 0.004 U/ml BLM. Significantly lower chromosome damage was found only in lymphocytes from children who, independently of the initial acute exposure to ionizing radiation, still showed a lJ7Cs internal contamination, due to persistent continuous exposure to low doses of radiation. The present results indicate that past exposure to acute high dose of ionizing radiation does not interfere with resistance to BLM which is related to internal contamination.

Specific antibodies protect gamma-irradiated mice against Francisella tularensis infection

Microbial Pathogenesis, 2012

The role of antibodies in the course of Francisella tularensis (F. tularensis) infection is still a subject of debate. The understanding of the poorly described role of humoral immunity is more than important for the effort to develop effective prophylactic procedure against the infection with Francisella virulent strains. We utilized the model of gamma-irradiated mice for the studies of the protective role of anti-F. tularensis antibodies in order to partially eliminate cellular responses. The model of gamma-irradiated mice can also demonstrate the responses of immunocompromised host to intracellular bacterial infection. The gamma-irradiation by doses greater than 3 Gy completely impairs the resistance to infection and causes a disbalance of cytokine production in mice. In this study, we demonstrate that passive transfer of immune sera protected irradiated mice against subsequent infection with strains of F. tularensis subsp. holarctica. Naïve mice of BALB/c or C3H/CBi strains were subjected to passive transfer of sera obtained from immunized mice with live vaccine strain (LVS) F. tularensis LVS, F. tularensis subsp. holarctica strain 15, heat-killed F. tularensis LVS, or heat-killed strain 15 two hours before infection with lethal doses of LVS or strain 15. The passive transfer of sera obtained from immunized mice conferred full protection of naïve unirradiated as well as sublethally irradiated mice against low lethal doses of infection with F. tularensis LVS or strain 15, in all variants of the experiments. In addition, the passively protected mice that survived the primary infection with F. tularensis LVS were protected also against further secondary challenge with a highly virulent strain of F. tularensis subsp. tularensis SchuS4. Moreover, the first evidence of combination of successful passive transfer of immunity by specific antisera and subsequent active immunization of immunocompromised animals is demonstrated. In summary, we demonstrate that B cell-mediated effector responses together with the induction of T cellmediated immunity both play an important role in naïve and also in immunocompromised mice and this fact it would be appropriate to take into the account in the design of new vaccines.

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.