Trypanosoma brucei: influence of host strain and parasite antigenic type on infections in mice

Inbred mice were infected with cloned populations of Trypanosoma brucei brucei Lister S42 under carefully controlled conditions. The course of infection was found to depend both on host strain and the antigenic type of the infecting organisms. The two antigenic types used, “NIM2” and “NIM6” had differing virulence for (CBA/H × C57BL/6)F₁ mice, and when mice were infected with parasites of one clone, trypanosomes of the other type frequently appeared after the initial population had been eliminated. Different mouse strains had varying susceptibility to clone NIM6. In most cases there was an inverse relation between the survival time and the parasite load during the first peak of parasitemia. The differences in resistance to T. brucei were unrelated to H-2 haplotype: C57BL/6 and (CBA/H × C57BL/6)F₁ were most resistant, CBA/H, BALB/c and DBA/2 less so, and C3H/He most susceptible.     

Trypanosoma cruzi: role of the immune response in the natural resistance of inbred strains of mice.

Nine inbred strains of mice were challenged with 10⁴ or 10⁵ trypomastigotes of the Brazil strain of Trypanosoma cruzi. A spectrum of resistance was evident ranging from highly susceptible strains, e.g., C3H, which developed high parasitemias and died within 3 to 4 weeks, to resistant strains, e.g., C57BL/10, which developed low parasitemias and survived. Impairment of the immune system in resistant C57BL/10 mice by X-irradiation, splenectomy, or treatment with silica led to high, often fatal parasitemias. Athymic nude mice, in particular, attained exceptionally high parasitemias before dying. The immune response appears to be necessary for survival and to play a role in the natural resistance of some mouse strains by effectively eliminating parasites and minimizing parasitemia. Using congenic strains of mice, it was shown that the principal genetic determinant of resistance is not associated with their H-2 haplotype.     

Brugia malayi: establishment in inbred and outbred strains of mice

Immunocompetent mouse model for human filarial parasite Brugia malayi is urgently required in view of the paucity of commercial reagents for other susceptible rodent viz. mastomys and gerbil. Genes within the major histocompatibility complex have been reported to influence the susceptibility of mouse to helminth parasites. Attempts have therefore been made in the present investigation to experimentally infect various inbred strains of mice viz. NZB/BINJ, BALB/c, AKR, C(3)H, and SJL/J with H-2 haplotype (H-2: d, d, k, k, s, respectively) and outbred strains of mice viz. Parks and Swiss. Findings indicate that susceptibility of mice to B. malayi is strain associated. This is the first report on the successful completion of full developmental cycle of subperiodic B. malayi in NZB/BINJ, an immunocompetent mouse strain. In some of the other strains, partial development or low degree of establishment of worms was observed.     

Trypanosoma musculi with Trichinella spiralis or Heligmosomoides polygyrus: concomitant infections in the mouse

Inbred mice infected with Trypanosoma musculi displayed wide variations in peak blood parasitemia. The most susceptible mice were C3H and A strain, while Balb/c, C57B1/6, and the related congenic B10 strains were the most resistant. The effect of an intestinal infection with either Trichinella spiralis or Heligmosomoides polygyrus on proliferation of T. musculi was investigated. T. spiralis infections given at the same time or up to 45 days before a T. musculi infection always caused an increase in blood parasitemia in C3H mice. Maximum increases were observed when T. spiralis infections preceded T. musculi by 5-10 days. In all mouse strains examined, dual infections increased maximum parasitemia by two- to four-fold, regardless of the degree of resistance of that mouse strain to either T. musculi or T. spiralis. This suggested that the immunological "cost" of a T. spiralis infection was the same for strains that were strong or weak responders to a primary infection with T. spiralis. In contrast, infection with H. polygyrus did not promote T. musculi parasitemia over the level of a single infection. The increase in blood parasitemia in T. spiralis-infected mice was largely due to the intestinal adult worm, but migratory larvae and mature muscle larvae also stimulated increased parasitemias. The increase in parasitemia was proportionate to the dose of T. spiralis, and the sex of the host did not affect the blood trypanosome level.     

Susceptibility of inbred mouse strains to infection with three species of Metagonimus prevalent in the Republic of Korea

Susceptibility of inbred mouse strains to Metagonimus yokogawai, Metagonimus miyatai, and Metagonimus takahashii infections was studied using BALB/c, ddY, C57BL/6J, C3H/HeN, and A/J mice, with H-2 haplotypes d, s, b, k, and a, respectively. Two hundred metacercariae were orally fed to each mouse, and the worm recovery rates (WRR), worm dimensions, and intrauterine egg numbers were measured at days 3, 7, 14, 21, and 28 postinfection (PI). On day 14 PI, the WRR of M. yokogawai was highest in ddY mice (average, 62.2%); those of M. miyatai and M. takahashii were highest in ddY (19.5%) and BALB/c mice (10.4%), respectively; worm maturation was best in C3H/HeN (M. yokogawai), C57BL/6J (M. miyatai), and ddY mice (M. takahashii). All mouse strains showed higher susceptibility to infection with M. yokogawai than with M. miyatai or M. takahashii. The results show that susceptibility of mice to Metagonimus infection varies according to mouse strain and parasite species but is suggested to be independent of the mouse H-2 haplotype.     

GENETIC RELATIONSHIPS BETWEEN PARASITE VIRULENCE AND TRANSMISSION IN THE RODENT MALARIA PLASMODIUM CHABAUDI

Many parasites evolve to become virulent rather than benign mutualists. One of the major theoretical models of parasite virulence postulates that this is because rapid within-host replication rates are necessary for successful transmission (parasite fitness) and that virulence (damage to the host) is an unavoidable consequence of this rapid replication. Two fundamental assumptions underlying this so-called evolutionary trade-off model have rarely been tested empirically: (1) that higher replication rates lead to higher levels of virulence; and (2) that higher replication rates lead to higher transmission. Both of these relationships must have a genetic basis for this evolutionary hypothesis to be relevant. These assumptions were tested in the rodent malaria parasite, Plasmodium chabaudi, by examining genetic relationships between virulence and transmission traits across a population of eight parasite clones isolated from the wild. Each clone was injected into groups of inbred mice in a controlled laboratory environment, and replication rate (measured by maximum asexual parasitemia), virulence (measured by live-weight loss and degree of anemia in the mouse), and transmission (measured by density of sexual forms, gametocytes, in the blood and proportion of mosquitoes infected after taking a blood-meal from the mouse) were assessed. It was found that clones differed widely in these traits and these clone differences were repeatable over successive blood passages. Virulence traits were strongly phenotypically and genetically (i.e., across clones) correlated to maximum parasitemia thus supporting the first assumption that rapid replication causes higher virulence. Transmission traits were also positively phenotypically and genetically correlated to parasitemia, which supports the second assumption that rapid replication leads to higher transmission. Thus, two assumptions of the parasite-centered trade-off model of the evolution of virulence were shown to be justified in malaria parasites.     

Endothelial cell changes are associated with pulmonary edema and respiratory distress in mice infected with the WA1 human Babesia parasite.

A C3H/HeN mouse model was established to study the pathogenesis of the human babesial parasites, WA1 and Babesia microti. To evaluate the course of parasitemia and the associated lesions, mice were inoculated intraperitoneally with either WA1-infected, B. microti-infected, or uninfected hamster red blood cells. WA1-infected mice developed dyspnea and moderate parasitemias, after which death occurred. Babesia microti-infected mice experienced low parasitemias with no apparent morbidity or mortality. WA1-infected mice were thrombocytopenic but not anemic. Hemograms for B. microti-infected mice were similar to controls. Postmortem examination of WA1-infected mice revealed prominent lesions in the lungs, including pulmonary edema and intravascular margination of leukocytes. No pulmonary changes were detected in B. microti-infected mice. Blood gas measurements of WA1-infected mice showed reduced oxygen saturation and pH, and increased carbonic acid compared to controls, indicating hypoxia and respiratory acidosis. Ultrastructure studies of WA1-infected lungs showed hypertrophied endothelial cells containing transcellular channels associated with protein-rich intra-alveolar fluid. Endothelial cell activation was demonstrated by an upregulation of intercellular adhesion molecule-1 in the lungs of WA1-infected mice. The results suggest that recruitment of inflammatory cells to the lungs in WA1-infected mice induces endothelial cell alterations, leading to pulmonary edema and acute respiratory failure.     

Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major

C3H/HeN mice that are naturally resistant to cutaneous disease and systemic infections with the protozoan parasite, Leishmania major, were treated at the time of infection, and weekly thereafter, with mouse anti-rat IFN-gamma mAb or an irrelevant antibody of similar isotype. Anti-IFN-gamma-treated mice developed cutaneous lesions; parasites spread to the regional lymph nodes and then metastasized to spleens and livers. The course of disease in these animals was similar to that of genetically susceptible BALB/c mice. Two exceptions in the pathology of L. major infections were noted between BALB/c and anti-IFN-gamma-treated C3H/HeN mice: 1) BALB/c mice died of systemic complications, whereas C3H/HeN mice did not, and 2) multinucleated giant cells were observed in lymph nodes and spleens of infected BALB/c mice, whereas these cells were not observed in infected C3H/HeN mice. Control mice, those treated with either saline or irrelevant antibody of the same isotype as the anti-IFN-gamma monoclonal, showed no evidence of cutaneous disease (development of footpad lesions) or systemic infection (by histopathology). Total abrogation of the natural resistance of C3H/HeN mice could be achieved by treatment with as little as 0.5 mg/mouse/wk of anti-IFN-gamma antibody, or by a single dose of 1 mg/mouse anti-IFN-gamma antibody administered at the time of parasite inoculation. If antibody treatment was delayed for as little as 1 wk after parasite inoculation, the infections in treated animals resembled that of untreated or control antibody-treated mice: no cutaneous lesions (by footpad swelling or viable counts of leishmania in footpad tissue) or systemic disease (by microscopic analysis of touch preparations of internal organs, and histopathology of same). The production of IFN-gamma during the initial interaction of the parasite and host cells appears to be a major component of genetic control of natural resistance to infection with L. major in C3H/HeN mice.     

Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice.

Groups of mice from genetically defined inbred strains were infected genitally with a pathogenic human strain of Chlamydia trachomatis and their subsequent fertility was compared. The CBA, C3H (H-2o) and C3H/He-mg (H-2k) mice were less fertile than control mice, at least up to 6 months after infection. In contrast, fertility was not impaired in BALB/c mice or in congenic BALB/K mice, which had the H-2k haplotype. Reduced fertility was paralleled by the extent of histological oviductal inflammation in mice of each strain. No salpingitis was seen 21 days after infection in the BALB strains, but lesions were apparent in CBA and C3H strains up to about 70 days after inoculation and these sometimes developed into hydrosalpinges. These results indicate that susceptibility to chlamydial salpingitis and subsequent infertility is under genetic control. This control was not simply associated with the major H-2 gene complex, as mouse strains of the same haplotype (H-2k) differed in susceptibility. The fertility of BALB/c (H-2d) and BALB/K (H-2k) strains was no different from that of controls, and congenic C3H mice of differing H-2 haplotypes (H-2k and H-2o) showed reduced fertility. Although all the infected F1 (BALB/K x C3H/He-mg) mice produced litters at the same rate as untreated controls, the litters were considerably smaller. This was due to the occurrence of unilateral pregnancies in the mice inoculated under the ovarian bursae and possibly also to early fetal death in mice inoculated directly in the uterus. These findings emphasize the importance of early diagnosis and treatment of infection of the lower genital tract of women.     

Non-antibody-mediated control of parasitemia in acute experimental Chagas' disease

There appear to be two phases in the control of parasitemia in acute Chagas' disease in the mouse. The first phase occurs during the first few weeks after infection and control is achieved through a thymus-dependent, antibody-independent mechanism. Challenge of B cell-suppressed C3H and F1 (C57BL/6 X C3H) mice with the Brazil strain of Trypanosoma cruzi led to a course of parasitemia for the first 3 wk after infection similar to that seen in normal C3H or F1 mice and markedly lower than the parasite levels observed in the blood of nu/nu mice. Challenge of BXH-2 recombinant inbred mice resulted in a course of parasitemia similar to that seen in nu/nu mice up to day 16 despite the production of normal levels of antibody. The BXH-2 mice lack the ability to effect the early control of parasitemia. The second phase begins several weeks after infection with the rise in antibody titer, and the control is exerted through an antibody-mediated mechanism. In all B cell-suppressed mice, an inexorable rise in parasitemia occurred up to the time of death, which suggests that antibody is important for the eventual clearance of parasites from the blood. A comparison of the IgM and IgG antibody titers to T. cruzi in a series of resistant and susceptible strains showed that there was no correlation between the appearance of specific antibody or antibody titers and the levels of parasitemia observed. The level of parasitemia attained in the late acute phase may be primarily determined by the extent of parasite proliferation in the early acute phase.     

Plasmodium chabaudi chabaudi: effect of low parasitemias on immunity in CB6F1 mice.

We examined the effect that low parasitemias have on the immune response of CB6F1 mice infected with Plasmodium chabaudi chabaudi AS. Ascending parasitemias were stopped by chloroquine treatment when they were between 1.6 and 9.4%. Mice that suffered low parasitemias developed good immunity to homologous reinfection but, contrary to what happened in mice that suffered full parasitemias, they did not develop immunity to heterologous reinfection with Plasmodium yoelii 17XL. Total IgG antiparasite antibody responses were similar in mice that suffered low or full parasitemia, both in primary infection and after reinfection. At the level of isotypes, IgM, IgG1, IgG2b, and IgG3 responses were similar in mice that suffered low or full parasitemias, but after reinfection, mice that suffered low parasitemias responded with higher levels of IgG2a than mice that suffered full parasitemias. Mice that suffered low parasitemias did not have splenomegaly but their immunity to homologous reinfection was diminished after splenectomy in a manner similar to that of splenectomized mice that suffered full parasitemia. CB6F1 mice can develop homologous immunity even if exposed to low parasitemias but cannot develop heterologous immunity unless exposed to high parasite loads.     

Keratinocytes synthesize Ia antigen in acute cutaneous graft-vs-host disease

Keratinocytes express la antigen (Ia) during cutaneous graft-vs-host disease (GVHD); it is, however, unclear whether this Ia is adsorbed from alloactivated donor lymphocytes or from Ia-bearing host Langerhans cells (LC), or whether it is actively synthesized by host keratinocytes. We therefore sought to determine the origin of keratinocyte Ia in a murine model of GVHD. Lethally irradiated C3H/He (H-2k) mice developed characteristic histopathologic changes of acute cutaneous GVHD 7 days after injection of BALB/c (H-2d) bone marrow and spleen cells, and expressed keratinocyte Ia of host (Iak) but not donor (Iad) origin in immunofluorescence studies. To determine whether the Ia was synthesized by keratinocytes or adsorbed from host LC, we investigated GVHD that was induced in chimeric mice. Parental strain A mice were made chimeric by lethal irradiation and reconstitution with (A X B)F1 bone marrow cells as follows: (BALB/c X C3H/He)F1 (H-2d,k) leads to C3H/He (H-2k), B6C3F1 (H-2b,k) leads to C57BL/6 (H-2b), and B6C3F1 (H-2b,k) leads to C3H/He (H-2k). After 3 mo, the LC in the skin of these chimeric mice were mainly of F1 haplotype. The chimeric mice were again lethally irradiated and injected with marrow and spleen cells from a third strain of mouse (C57BL/6, H-2b or BALB/c, H-2d) histoincompatible with both F1 parental strains. In the ensuing GVHD, the chimeric recipients only expressed keratinocyte Ia syngeneic to the original haplotype of the animal (strain A), despite the fact that the majority of their LC were derived from F1 marrow and expressed Ia of both F1 parental strain haplotypes (strains A and B). Together, these findings indicate that keratinocyte Ia in GVHD is synthesized by keratinocytes and is not derived from donor lymphocytes or adsorbed from host LC.     

Plasmodium berghei: Isolation and maintenance of an irradiation attenuated strain in the nude mouse

An attenuated strain of malaria causing limited parasitemia in mice was derived from a highly virulent strain of Plasmodium berghei (NK65) which produced 100% lethality in mice. A pool of mouse blood infected with the original highly virulent P. berghei was exposed to 40 Krad irradiation and parasites were inoculated into nude mice as well as into thymus competent normal littermates. Thymus competent mice showed no parasitemia, while one out of the five nude mice inoculated with the irradiated parasites developed a slow and progressive parasitemia. These parasites induced a self-limiting parasitemia in thymus competent mice, even when a large inoculum was administered. Maintenance of the low virulence strain required passage through nude mice. After 50 passages at two weekly intervals, reversion to virulence did not occur. A single vaccination with the attenuated strain induced immunity in mice against a challenge inoculation with the original virulent strain. Specific IgG persisted at high titer for more than 9 weeks in mice receiving a single inoculation of the attenuated strain.     

Immunization with extracellular vesicles excreted by Toxoplasma gondii confers protection in murine infection,activating cellular and humoral responses

The study aim was to analyze whether microvesicles and exosomes, named extracellular vesicles (EVs), purified from Toxoplasma gondii are able to stimulate the protective immunity of experimental mice when administered, as challenge, a highly virulent strain. EVs excreted from T. gondii tachyzoites (RH strain) were purified by chromatography and used for immunization assays in inbred mouse groups (EV-IM). Chronic infected (CHR) and naive (NI) mice were used as control groups, since the immune response is well known. After immunizations, experimental groups were challenged with 100 tachyzoites. Next, parasitemias were determined by real-time PCR (qPCR), and survival levels were evaluated daily. The humoral response was analyzed by detection of IgM, IgG, IgG1 and IgG2a, and opsonization experiments. The cellular response was evaluated in situ by immunohistochemistry on IFN-γ, IL-10, TNF-α and IL-17 expression in cells of five organs (brain, heart, liver, spleen and skeletal muscles). EV immunization reduced parasitemia and increased the survival index in two mouse lineages (A/Sn and BALB/c) infected with a lethal T. gondii strain. EV-IM mice had higher IgG1 levels than IgM or IgG2a. IgGs purified from sera of EV-IM mice were able to opsonize tachyzoites (RH strain), and mice that received these parasites had lower parasitemias, and mortality was delayed 48 h, compared with the same results from those receiving parasites opsonized with IgG purified from NI mice. Brain and spleen cells from EV-IM mice more highly expressed IFN-γ, IL-10 and TNF-α. In conclusion, EV-immunization was capable of inducing immune protection, eliciting high production of IgG1, IFN-γ, IL-10 and TNF-α.     

Genetics of resistance to the African trypanosomes. IV. Resistance of radiation chimeras to Trypanosoma rhodesiense infection

The cellular bases of resistance to the African trypanosomes were examined in inbred mice. As part of these studies, reciprocal bone marrow cell transplants were performed between H-2 compatible mice which differ in relative resistance to Trypanosoma brucei rhodesiense infection. Survival times, parasitemias and IgM antibody responses to the surface antigen of the infecting variant type were measured in these semiallogeneic bone marrow chimeras. Relatively resistant C57BL/10 mice, intermediate A.By mice, and least resistant C3H.SW mice that were reconstituted after lethal irradiation with syngeneic bone marrow cells displayed resistance and immunity characteristic of the homologous donor strain. When C57BL/10 mice were reconstituted with C3H.SW mouse bone marrow cells they retained the ability to produce antibodies to trypanosome surface antigen but the antibody titers were significantly reduced. Control of parasitemia and mean survival time were reduced in these chimeras, but differed significantly from C3H.SW mice. A.By mice that received cells from C57BL/10 donors exhibited antibody responses and survival times similar to the C57BL/10 mice. Survival times of A.By mice given syngeneic cells or C3H.SW cells were the same, but the antibody responses of A.By mice given C3H.SW cells were lower than those of A.By mice given syngeneic cells. C3H.SW mice reconstituted with C57BL/10 bone marrow cells were capable of making antibodies and controlling parasitemia, in marked contrast to the absence of such responses in C3H.SW mice reconstituted with syngeneic cells. Survival times, however, were indistinguishable from those of C3H.SW mice given syngeneic cells. Thus, resistance to T. b. rhodesiense was shown for the first time to depend on donor bone marrow derived cells as well as upon radiation-resistant cells/factors associated with host genetic background. Also, parasite-specific IgM antibody responses seem to be regulated by a mechanism which does not depend on bone marrow derived cells alone, and the presence of such immune responses is not linked to survival time.     

Kinetics of expression of infectious ecotropic, xenotropic, and mink cell focus-forming murine leukemia virus after 5-iododeoxyuridine induction of cells from high- and low-leukemia mouse strains

Endogenous murine leukemia virus (MuLV) was induced with 5-iododeoxyuridine (IdUrd) from the high-leukemia mouse strain AKR and from two low-leukemia strains, C3H/He and BALB/c. A virus-free cell line from strain AKR readily gave rise to infectious, XC-positive MuLV upon treatment with IdUrd, whereas cells from strains C3H/He and BALB/c produced replication-deficient, XC-negative MuLV. IdUrd-induced cells also produced xenotropic and mink cell focus-forming MuLV. Xenotropic virus emerged at a higher titer from both AKR and BALB/c cells during two discrete time intervals, first at day 3 after induction and a second time during spread of the induced ecotropic MuLV. Xenotropic and mink cell focus-forming MuLVs were also produced by IdUrd-induced C3H/He cells but required another round of infection in Sc-1 cells for detection. The in vitro infectivity of endogenous ecotropic MuLV isolated by IdUrd induction from C3H/He cells correlated with pathogenicity in the Fv-1-compatible, leukemia-negative mouse strain NFS/N. Thus, the virulence of endogenous ecotropic MuLV may be an important factor in determining the leukemia incidence in these inbred strains of mice.     

Toxoplasma gondii: the vaccine potential of three trivalent antigen-cocktails composed of recombinant ROP2, ROP4, GRA4 and SAG1 proteins against chronic toxoplasmosis in BALB/c mice

Toxoplasmosis is one of the world's most widespread zoonoses caused by protozoan parasite Toxoplasma gondii. The development of an effective vaccine for controlling toxoplasmosis is an extremely important issue due to the serious clinical and veterinary outcomes of this parasitosis. The objective of this study was evaluation of vaccine potential of three trivalent subunit recombinant vaccines composed of rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 against chronic toxoplasmosis in BALB/c (H-2(d)) mice. All tested vaccines provided a partial protection against challenge with tissue cysts of the low virulence DX T. gondii strain, but the strongest level of protection was induced by the mixtures of both rhoptry proteins (rROP2 and rROP4) administered with the dense granule rGRA4 antigen or the main surface rSAG1 protein. The average parasite burden in these groups of vaccinated BALB/c mice was reduced by 84% and 77%, respectively, compared to the control PBS-injected animals. The vaccine-induced protection was correlated with the development of cellular and humoral immune responses demonstrated by the antigen-specific in vitro proliferation of spleen cells, the specific antigen-induced in vitro synthesis of Th1-type cytokines, IFN-γ and IL-2, and the generation of the high titers of systemic antigen-specific IgG1 and IgG2a antibodies. This study completed and confirmed our earlier investigations in C3H/HeJ (H-2(k)) and C57BL/6 (H-2(b)) mouse strains on the utility of the tested trivalent recombinant antigen-cocktails as potential vaccines against chronic toxoplasmosis and showed that particularly rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 protein-combinations are very effective in the development of a high level of protection irrespective of the genetic backgrounds and innate resistance to toxoplasmosis of the laboratory mice. It makes these two mixtures of recombinant antigens very promising for further experiments.     

Specificity of the mouse cytotoxic T lymphocyte response to adenovirus 5. E1A is immunodominant in H-2b, but not in H-2d or H-2k mice

The Ag specificity and MHC restriction of the CTL response to adenovirus 5 (Ad5) in three strains of mice, C57BL/10 (H-2b), BALB/c (H-2d), and C3H/HeJ (H-2k), were tested. Polyclonal Ad5-specific CTL were prepared by priming mice in vivo with live Ad5 virus followed by secondary in vitro stimulation of the spleen cells with virus-infected syngeneic cells. The Ad5-specific CTL were Db restricted in C57BL/10 and Kk restricted in C3H/HeJ. In BALB/c mice both Kd- and Dd/Ld-restricted CTL were detected. The polyclonal Ad5-specific CTL response in C57BL/10 mice is directed exclusively against the products of the E1A region, which comprises only 5% of the Ad5 genome. In BALB/c mice E1A is at best a very minor target Ag and in C3H/HeJ mice E1A is not recognized at all. Using the H-2 congenic mouse strains B10.BR (H-2k) and C3H.SW (H-2b) it was shown that the immunodominance of E1A is H-2 dependent. The 19-kDa glycoprotein encoded in the E3 region of Ad5, which binds to class I MHC in the endoplasmic reticulum and prevents its translocation to the cell surface, does not affect the specificity of the CTL response in C57BL/10 mice toward E1A. However, it affects the MHC restriction of the Ad5-specific response in BALB/c mice, selectively inhibiting generation of Kd-restricted CTL.     

Plasma levels of proteins of the alternative complement pathway in inbred mice that differ in resistance to Trypanosoma congolense infections.

Inbred BALB/c, A/J, and C57B1/6J mice were infected with Trypanosoma congolense (Trans Mara strain), clone TC13, and monitored for parasitemia, survival times, and plasma levels of complement components C3, C5, factor B, and factor H. Parasitemia was highest in BALB/c, intermediate in A/J, and lowest in C57Bl/6J mice. The mean survival times were 11.5 +/- 0.9, 23.8 +/- 2.3, and 119 +/- 26 days for BALB/c, A/J, and C57Bl/6J mice, respectively. Preinfection levels of factor H were significantly correlated with survival times (r = 0.7722, P less than 0.001). Marked differences were observed between the plasma levels of C3, factor B, and factor H in the 3 mouse strains following infection. Complement C5 levels showed the fewest changes. In the initial postinfection period, BALB/c mice had highest increases in the levels of the 4 complement proteins but also had the greatest declines toward the end of the infection. Factor H levels showed a biphasic increase in BALB/c and C57Bl/6J, but not in A/J mice, with peaks at days 3 and 9. Complement C3 levels declined in all mice toward the terminal stage of the disease. In the late stages of infection, factor B levels markedly decreased in BALB/c but significantly increased in C57Bl/6J mice. Factor B levels measured at the terminal stages in BALB/c, A/J, and C57Bl/6J were correlated positively with their respective survival times (r = 0.714, P less than 0.01). The results suggest that genetic differences in the alternative complement pathway might affect the resistance to T. congolense infections.     

用hu-RBC-SCID小鼠分离鉴定献血者巴贝斯样原虫

目的用人红细胞(RBC)替代SCID小鼠自身血循环红细胞而建立的人化小鼠模型,即hu-RBC-SCID模式小鼠,分离并鉴定献血者中隐性人巴贝斯虫病原的感染,确定输血患者的感染来源.方法去除NOD/shi-scid小鼠自身血循环红细胞,辅以肌肉注射兔抗小鼠血红蛋白生成素血清和大鼠抗小鼠RBC单克隆抗体,用人O型红细胞注入NOD/shi-scid小鼠血循环中,建成hu-RBC-SCID模式小鼠,接种献血者的RBC.结果接种献血者的RBC的hu-RBC-SCID模式小鼠的RBC中,出现巴贝斯原虫,并大量增殖,最高达到40%,经形态学、PCR等方法鉴定病原为 Babesia microti 样原虫,与患者的一致.结论 hu-RBC-SCID模式小鼠证实,患者确因输血感染;hu-RBC-SCID模式小鼠是人巴贝斯原虫研究理想的动物模型.