Foreign serum-induced bile duct lesion (BDL) in athymic BALB/c nude mice

To investigate a role of cellular immunity in foreign serum-induced bile duct lesion (BDL) in mice, athymic BALB/c nude (nu/nu) mice were intraperitoneally injected with swine serum (SS) twice a week up to 8 weeks and were compared with euthymic BALB/c heterozygote (nu/+) and wild-type (+/+) mice treated with SS in the same way for 4 weeks. All immunized nu/+ and +/+ mice developed marked BDL, and their sera showed high anti-SS IgE and IgG1 antibody titers, whereas no immunized nu/nu mice developed lesions, and their sera showed no elevation of antibody titers. Next, nu/nu mice were reconstituted with splenocytes derived from nu/+ mice, and then were intraperitoneally injected with SS twice a week for 3 weeks. Most of the reconstituted nu/nu mice developed BDL, and their sera showed the elevation of anti-SS IgE and IgG antibody titers. These results suggest that cellular immunity may play a pivotal role in the pathogenesis of swine serum-induced BDL.     

Mycoplasma pulmonis arthritis in congenitally athymic (nude) mice. Clinical and biological features

Congenitally athymic BALB/cA nu/nu mice were employed to elucidate the role of the thymus in experimental Mycoplasma pulmonis strain m53 infection, and nu/+ mice were used for comparison. Chronic polyarthritis was frequently produced in both of nu/nu and nu/+ mice by intravenous injection of the organisms. Macroscopically, nu/nu mice developed severer arthritis and a much lower grade of resolution than nu/+ mice. Periarticular abscess, conjunctivitis, and emaciation were observed in some of the nu/nu mice, but not in the nu/+ mice. Mycoplasmas were isolated from joints and other tissues (including periarticular abscesses and eyelids) of infected nu/nu mice at higher frequencies as well as in greater quantities, and did not show any elimination trends for at least 20 weeks after inoculation. However, nu/+ mice, mycoplasmas were almost exclusively located in joints, and distribution of organisms to the other organs disappeared soon after the infection. Increases in complement-fixing antibody titers were not related to the inhibition of mycoplasmal spread. Thymus-dependent functions that may in some way prevent growth and spread of mycoplasmas in mice are discussed.     

Effects of probiotic bacteria on humoral immunity to Candida albicans in immunodeficient bg/bg-nu/nu and bg/bg-nu/+ mice

Germfree beige-nude ( bg/bg-nu/nu) and beige-heterozygous ( bg/bg-nu/+) mice were colonized with a pure culture of Candida albicans or with a probiotic bacterium (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, or Bifidobacterium infantis). Probiotic-colonized mice were subsequently challenged orally with C. albicans. The effect of prior colonization with probiotic bacteria on the antibody responses of the immunodeficient mice to alimentary tract colonization with C. albicans was compared to the antibody responses of the gnotobiotic mice colonized only with C. albicans. This study demonstrated that, although the probiotic bacteria did not induce a vigorous antibody response to their own antigens, they altered the antibody responses of mice to C. albicans. In T cell competent bg/bg-nu/+mice, B. infantis enhanced and focused IgG1, IgG2A, and IgA responses to C. albicans antigens. Some of the probiotic bacteria also enhanced the IgG1 and IgG2A antibody responses of bg/bg-nu/nu mice to C. albicans antigens. This study not only shows the value of gnotobiotic animal models in demonstrating that probiotic bacteria can affect the capacity of mice to form antibodies to C. albicans, but it also points out their usefulness in comparing the capacity of different probiotic bacteria to produce beneficial health effects in mice.     

Nematospiroides dubius: susceptibility to infection and the development of resistance in hypothymic (nude) BALB/c mice.

BALB/c-nu/nu mice and their intact nu/+ littermates are equally susceptible to infection with third-stage larvae of Nematospiroides dubius. Unlike their heterozygous littermates, however, the nu/nu mice are unable to form ganulomata in the intestinal wall and become only partially resistant to rechallenge. Following two or more infections, nu/nu mice maintain a high burden of adult intestinal worms, whereas worms are lost from immune nu/+ mice. Studies in T cell-injected nu/nu mice suggest that a full complement of T cells is needed to develop maximum resistance against the infective third-stage larvae and to expel adult worms. Measurement of serum immunoglobulin levels indicate that infected nu/+ mice have very high levels of IgG1 whereas the levels of IgG2a are reduced. In infected T cell-injected nu/nu mice, IgG1 levels increase with the number of T cells injected, whereas IgG2a levels are variable but always higher than in infected nu/+ mice.     

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.     

Activation of a functional idiotype network response by monoclonal antibody specific for a virus (M-MuLV)-induced tumor antigen

BALB/c mice were injected with IgM mAb specific for Moloney murine leukemia virus (M-MuLV)-determined cell surface Ag in an attempt to inhibit Moloney sarcoma growth. The monoclonal IgM significantly inhibited sarcoma growth when given to the mice after inoculation with Moloney murine sarcoma/leukemia virus, and also potentiated the in vivo antibody response specific for M-MuLV Ag. These responses were significantly greater than the primary response to the virus alone in age- and sex-matched control mice, and were also seen in mice which were injected with the IgM antibody only and not with virus, suggesting that an Ag-independent mechanism may be involved. The M-MuLV-specific serum antibody responses induced by the monoclonal IgM, with or without prior virus inoculation, were predominantly of the IgG1 isotype, with some IgG2a; no other isotypes were found to have titers significantly higher than in the normal response to virus alone. M-MuLV-specific IgG1 was detected only in mice injected with monoclonal IgM, and not in the response to virus alone. The same sera also had high titers of anti-idiotypic antibodies, (Ab2), as well as anti-anti-idiotypic antibodies (Ab3). It appears, therefore, that passive immunization with M-MuLV-specific IgM mAb activates an idiotypic network, which results in both Ab2 and Ab3 responses; the M-MuLV-specific response may be considered a subset of Ab3.     

Anti-mu induces lymphoma in germfree congenitally athymic (nude) but not in heterozygous (nu/+) mice

To further our understanding of the role of host immunity in the development of lymphoid neoplasia, groups of germfree BALB/c nude and nu/+ mice were either followed unmanipulated or were treated, beginning at birth, with anti-mu, normal goat IgG or with lipopolysaccharide (LPS). The survival and development of neoplasia of all groups of animals were monitored up to 2 yr. Nude mice, under germfree and specific pathogen-free (spf) conditions, had a higher incidence of lymphoid neoplasia and reduced survival when compared to nu/+ littermates. The incidence of lymphoid tumors in nude mice under spf or germfree conditions was 7.2 and 8.7%, respectively, in comparison to 0% in nu/+ animals. Treatment of germfree nude mice with anti-mu, but not with goat IgG, increased the incidence of lymphoid tumors to 39%. Anti-mu did not significantly change the incidence of lymphoid neoplasia in nu/+ animals. Treatment of nu/nu and nu/+ mice with LPS, however, led to a several-fold increase in the appearance of neoplasia, to values of 25.4% in nude and 10% in nu/+ mice. Lymphoid neoplasia found in either unmanipulated, anti-mu, or IgG-treated germfree or spf mice included Thy-1.2+, surface IgM+, and IgG+ tumors. In contrast, all the lymphomas found in LPS-treated mice were surface IgM+. Thus, whereas LPS may have generated a relatively homogeneous group of tumors, anti-mu may have randomly increased the normal incidence of spontaneous tumors. Moreover, although there was significant variation in the histologic appearance of tumors, both within treatment groups as well as in different areas of the same animal, only LPS-treated mice were regularly noted to have distant nonlymphoid involvement, with lesions found in liver, lung, and kidney. In contrast, the incidence of nonlymphoid neoplasia was similar and was less than 2.5% in all groups.     

Production of BSF-1 during an in vivo, T-dependent immune response

BSF-1, a cytokine produced by some T lymphocyte tumors, has been shown to act with anti-Ig antibodies to stimulate B lymphocyte proliferation, to independently induce resting B lymphocytes to increase their expression of surface Ia antigen, and to induce some activated B lymphocytes to differentiate into IgG1- or IgE-secreting cells. To determine whether BSF-1 might be secreted by normal lymphoid cells in the course of a physiologic immune response, BALB/c mice were injected with an affinity-purified goat antibody to mouse IgD (GaM delta), which induces the generation of a large, polyclonal T-dependent IgG1 response; 4-hr culture supernatants of spleen cells from these mice were prepared, and these supernatants were assayed for BSF-1 activity by analyzing their ability to induce BALB/c nu/nu spleen cells to increase their expression of cell surface Ia in vitro. Culture supernatants of unfractionated spleen cells removed from mice 4 to 8 days after GaM delta antibody injection induced substantial increases in B lymphocyte surface Ia expression; these increases were blocked by a monoclonal anti-BSF-1 antibody. Culture supernatants of spleen cells from untreated BALB/c mice or from untreated or GaM delta antibody-treated BALB/c nu/nu mice induced small to moderate increases in B cell surface Ia expression, and GaM delta antibody itself induced large increases in B cell surface Ia expression; however, these increases were not significantly blocked by a monoclonal anti-BSF-1 antibody. A culture supernatant of T cell-enriched spleen cells from untreated mice induced small increases in B cell surface Ia expression that were inhibited by anti-BSF-1 antibody, as was the larger increase in B cell Ia expression induced by a culture supernatant of T cell-enriched spleen cells from mice sacrificed 3 days after GaM delta injection. On the other hand, T cell-depleted spleen cells from BALB/c mice injected with GaM delta antibody 7 days before sacrifice failed to generate culture supernatants with BSF-1 activity. Supernatants prepared from spleen cells taken from untreated mice or mice treated with GaM delta antibody 1 to 3 days before sacrifice did not block the ability of purified BSF-1 to induce an increase in B cell surface Ia expression, and thus did not contain inhibitors of BSF-1 activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nasal Immunization of Mice with Human Papillomavirus Type 16 Virus-Like Particles Elicits Neutralizing Antibodies in Mucosal Secretions

To specifically induce a mucosal antibody response to purified human papillomavirus type 16 (HPV16) virus-like particles (VLP), we immunized female BALB/c mice orally, intranasally, and/or parenterally and evaluated cholera toxin (CT) as a mucosal adjuvant. Anti-HPV16 VLP immunoglobulin G (IgG) and IgA titers in serum, saliva, and genital secretions were measured by enzyme-linked immunosorbent assay (ELISA). Systemic immunizations alone induced HPV16 VLP-specific IgG in serum and, to a lesser extent, in genital secretions but no secretory IgA. Oral immunization, even in the presence of CT, was inefficient. However, three nasal immunizations with 5 μg of VLP given at weekly intervals to anesthetized mice induced high (>10⁴) and long-lasting (>15 weeks) titers of anti-HPV16 VLP antibodies in all samples, including IgA and IgG in saliva and genital secretions. CT enhanced the VLP-specific antibody response 10-fold in serum and to a lesser extent in saliva and genital secretions. Nasal immunization of conscious mice compared to anesthetized mice was inefficient and correlated with the absence of uptake of a marker into the lung. However, a 1-μg VLP systemic priming followed by two 5-μg VLP intranasal boosts in conscious mice induced both HPV16 VLP-specific IgG and IgA in secretions, although the titers were lower than in anesthetized mice given three intranasal immunizations. Antibodies in serum, saliva, and genital secretions of immunized mice were strongly neutralizing in vitro (50% neutralization with ELISA titers of 65 to 125). The mucosal and systemic/mucosal HPV16 VLP immunization protocols that induced significant titers of neutralizing IgG and secretory IgA in mucosal secretions in mice may be relevant to genital HPV VLP-based human vaccine trials.     

Cells with natural killer activity in the cerebrospinal fluid of normal mice and athymic nude mice with acute Sindbis virus encephalitis

Sindbis virus causes an acute, nonfatal inflammatory encephalitis in weanling BALB/c mice. Mononuclear inflammatory cells are present in the cerebrospinal fluid (CSF) as well as in the parenchyma of the brain. Both aspects of this inflammatory response were eliminated by treatment with cyclophosphamide. Athymic nude (nu/nu) mice developed no inflammation in the brain, but did develop a CSF pleocytosis that peaked on day 2 after infection. The time course of the appearance of cells in the CSF was earlier in nu/nu mice than their heterozygote (nu/+) littermates. The pleocytosis in nu/nu mice reached a peak on day 2, whereas in nu/+ mice the peak was on day 4, as it is in normal BALB/c mice. To determine whether some of the CSF cells in nu/nu mice may be natural killer (NK) cells, NK activity was measured in a 4-hr assay by using a YAC-1 target cell. NK cell activity in the spleen and peripheral blood was induced by infection with Sindbis virus in nu/nu mice with a similar time course to that of nu/+ mice (peak 1 day after infection). CSF from nu/nu mice had NK activity present 2 days after infection that was greater than that present in either the peripheral blood or spleen. BALB/c and nu/+ mice had insufficient cells present for assay at day 2, but BALB/c mice had NK activity present in the CSF 3 and 5 days after infection that exceeded that in the peripheral blood or spleen. Brain interferon was detectable on day 1 in nu/nu mice, but not until day 2 in nu/+ mice even though the amounts of brain virus were the same in the two groups at all time points. It is concluded that cells with NK activity contribute to the CSF pleocytosis induced by acute Sindbis virus encephalitis.     

Isotype profiles of anti-influenza antibodies in mice bearing the xid defect.

The humoral response to influenza A/PR8 virus was examined in the CBA/N and C3J.xid strains of mice, both of which bear an X-linked genetic defect (xid), and in strains lacking this defect. Hemagglutination-inhibiting antibody titers and measurement of virus-specific antibodies by solid-phase radioimmunoassay indicated that the xid defect does not impair the production of an adequate anti-influenza antibody response. However, investigation of the isotypes of PR8 virus-specific antibodies disclosed a relative decrease in the levels of IgG3 and IgG1 in the xid-bearing strains. This was observed after both intraperitoneal immunization and aerosol infection. The isotype differences were not reflected in the susceptibility of these strains to influenza virus infection.     

Histopathological studies on experimental Cryptococcosis in nude mice

Cryptococcosis in nude (nu/nu) mice was examined histopathologically. In addition, effects of carrageenan and lymph node cell transfer againstCryptococcus infection were investigated. As controls, heterozygous littermates (nu/+mice) and mice of strain ddy (ddy mice) were employed.Each mouse was inoculated intravenously with 10⁵ yeast cells ofCryptococcus neoformans suspended in 0.2 ml phosphate-buffered saline. Two mice out of each group were sacrificed at appropriate intervals up to 25 days after inoculation and histopathological sections were prepared from them. They were stained with H & E and by PAS method. Histopathological characterristic in the brain was cyst formation with no cellular response. The brain was more severely in the nu/nu mice than in either the nu/+ or ddy mice. In the liver, there was a major difference in histopathological findings between the nu/nu and either of the other groups of mouse. In the nu/nu mice, cyst formation with no cellular response was induced, and on the contrary granuloma formation in the nu/+ and ddy mice. However, the granuloma formation was inhibited in the livers of the nu/+ and ddy mice by administration of carrageenan, and induced in the nu/nu mice by cell transfer. In the spleen and lymph nodes, lesions were severer in nu/nu mice than in either the nu/+ or ddy mice.These results suggested that the fungus' invasiveness of mice was strongly influenced by T-cell dependent mechanism.     

Immunologic abnormality in NZB/NZW F1 mice. Thymus-independent occurrence of B cell abnormality and requirement for T cells in the development of autoimmune disease, as evidenced by an analysis of the athymic nude individuals

Both NZB nu/+ and NZW nu/+ mice were microbially clean by cesarean section. The (NZB x NZW)F1 hybrid (NZB/W) nu/nu mice and nu/+ littermates were then generated by mating of NZB nu/+ with NZW nu/+mice under specific pathogen-free conditions. The female NZB/W F1 nu/nu mice did not develop autoimmune kidney disease, whereas all of nu/+ female littermates mice exhibited proteinuria and died of renal failure with a 50% survival time of 35 wk. Namely, nude mice had no signs of proteinuria up to the time of their death caused by other diseases rather than glomerulonephritis, and their mean survival time was greater than 45 wk. Nude mice had also no anti-ssDNA antibody in their serum. However, splenic B cells of NZB/W nude mice exhibited hyper-responsiveness to both LPS and B151-TRF2, a T cell-derived polyclonal B cell-stimulation factor, and produced large numbers of Ig-secreting cells and anti-TNP plaque-forming cells as well as anti-ssDNA antibody comparable to the nu/+ littermate mice. Interestingly, thymus-engrafted NZB/W nude mice developed autoimmune disease exemplified by the induction of anti-ssDNA antibody and proteinuria at approximately the same time as their nu/+ littermates. These results indicate that the B cell hyper-responsiveness found in NZB/W mice is apparently determined by the T cell-independent process, and T cells are obligatorily required for the development of autoimmune disease in NZB/W mice.     

Antigen-induced acceleration of shedding and replacement of B cell antigen receptors requires mature T cells

To determine which early and intermediate events in the response of antigen-binding B cells to a T-dependent antigen (sheep erythrocytes [SRC]) require T help, the antigen-induced changes in receptor turnover and surface IgD loss in BALB/c athymic nu/nu mice were compared with that of nu/+ littermates and +/+ BALB/c mice. Nonimmune SRC antigen-binding spleen B cells (ABC) from +/+, nu/+, and nu/nu BALB/c mice coexpressed IgM and IgD, and 85 to 95% retained receptors well when incubated for 2.5 hr in 100 micrograms/ml cycloheximide (which prevents receptor replacement). Also they were able to regain their ability to bind antigen by 18 hr after pronase treatment, but not by 2 hr. However, 5 days after in vivo immunization, 1) the proportion of ABC expressing surface IgD declined from around 90% to less than 50% in +/+ mice and nu/+ mice but not in nu/nu mice; 2) substantial recovery of antigen-binding occurred by 2 hr after pronase treatment in +/+ and nu/+ ABC but not in nu/nu ABC; and 3) when spleen cells were incubated in cycloheximide, uncompensated receptor shedding reduced +/+ and nu/+ ABC by around 80% but produced only about a 10% reduction in nu/nu ABC. Thus, although the ABC in nonimmune nu/nu mice appeared normal with respect to their surface Ig turnover and expression, they failed to undergo the normal antigen-induced loss of IgD or acceleration of surface Ig shedding and replacement, suggesting that these intermediate activation events require interaction with mature T cells. To determine whether this interaction had to occur during B cell development, during the development of the immune response, or during receptor shedding or replacement itself, cell transfer experiments were carried our wherein nu/+ T cells were transferred i.v. to nu/nu littermates 1 day before immunization with SRC. In the transfer recipients, pronase-treated day 5 ABC were then able to replace and shed their receptors at the accelerated rate, like ABC from +/+ and nu/+ mice. In contrast, the co-incubation of 5-day immune nu/+ T cells with nu/nu B cells did not alter the rate of shedding or replacement.     

Production of anti-Candida antibodies in mice with gut colonization of Candida albicans

BACKGROUND: Production of antibodies that are specific for allergens is an important pathological process in inflammatory allergic diseases. These contain the antibodies against antigens of Candida albicans, one of the normal microbial flora in an intestinal tract. We studied the effects of the prednisolone administration on the production of anti-Candida antibodies in the gastrointestinally C. albicans-colonized mice. METHODS AND MATERIALS: BALB/c mice, treated with antibacterial antibiotics to decontaminate indigenous intestinal bacterial flora, were inoculated intragastrically with C. albicans. The mice, in which C. albicans grows intestinally, were administered prednisolone to induce temporary immunosuppression. The Candida growth in their intestinal tract and their antibody response to Candida were examined. RESULTS: Antibiotic treatment allowed establishment of C. albicans gastrointestinal colonization, but did not cause subsequent systemic dissemination of C. albicans in all the animals. When these animals received an additional treatment with prednisolone, they showed a significantly higher population of C. albicans in their feces than those of animals treated with antibiotics alone, and the organisms were recovered even from their kidney. This systemic dissemination by C. albicans appeared to be temporal, because all the mice survived without any symptoms for more than 2 months. Examination of the serum titers of total immunoglobulin (Ig)E antibodies and specific IgE and IgG antibodies against Candida antigens demonstrated that titers of total IgE increased, partially by day 14 and clearly at day 27, in prednisolone-treated Candida-colonized mice. Without prednisolone treatment, an increment of the serum titer was scarcely observed. By day 27, corresponding to the increase of total IgE, the anti-Candida IgE and IgG titer increased in mice of the prednisolone-treated group. CONCLUSION: Administration of prednisolone to Candida-colonized mice can induce production of the IgG, IgE antibodies against Candida antigens, perhaps through temporal systemic dissemination of Candida from the intestinal tract.     

Serum antibody response of gnotobiotic athymic and euthymic mice following alimentary tract colonization and infection with Candida albicans

Colonization and infection evoked specific immunoglobulin responses to Candida albicans antigens in gnotobiotic nu/+ mice which appeared to correlate with clearance of infected mucosal surfaces (tongue and stomach). Conversely, colonized and infected nu/nu mice formed some IgM but no detectable IgG or IgA antibodies against C. albicans antigens. Although chronic mucosal infections of tongue and stomach persisted in nu/nu mice, they were able to resist overwhelming mucosal and systemic infections with C. albicans. Thus, C. albicans specific antibodies may play a role in clearance of mucosal candidiasis (tongue and stomach), but these antibodies do not appear to be necessary for protecting athymic mice against systemic candidiasis of endogenous origin.     

Thymus-independent induction and antigen-dependent recovery of idiotype-specific suppression

BALB/c nude (nu/nu) mice and euthymic (nu/+) littermates were treated as neonates with anti-T15 antibody and challenged at various ages with either a thymus-independent, PC-Brucella abortus (PC-BA), or thymus-dependent, PC-keyhole limpet hemocyanin (PC-KLH), form of phosphorylcholine (PC). Nu/nu mice challenged with PC-KLH received KLH-primed splenic T cells prior to immunization. Neither neonatally anti-idiotype-treated nu/+ nor nu/nu mice responded with the production of T15-positive anti-PC antibodies after challenge with either form of PC antigen. It is concluded that neither induction nor maintenance of a state of T15-specific suppression requires thymus-matured T cells. Recovery of anti-PC responsiveness in suppressed nu/+ or nu/nu mice was similar and was found to be related to the form of antigen used to elicit the response. Immunization with PC-KLH revealed a long-lasting unresponsiveness (up to 16 weeks). In contrast, immunization with PC-BA elicited a full anti-PC response as early as at 6.5 weeks of age.     

Defective resistance to Plasmodium yoelii in CBA/N mice.

The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice derived from CBA/N mice, a strain with an X-linked B cell defect. When infected with normally nonlethal Plasmodium yoelii, immune defective F1 male mice had higher parasitemias and more prolonged infections than normal F1 mice, as well as a 50% mortality rate. Before infection the plasma levels of IgM and IgG were lower in defective F1 males than normal F1 mice. The polyclonal IgM and IgG responses of infected abnormal F1 mice were delayed and lower in absolute magnitude than those of normal F1 mice. Furthermore, specific IgM and IgG anti-plasmodial antibody titers, as determined by radioimmunoassay, were depressed on day 12 in the defective F1 males. Although IgG titers approached those of the normal F1 mice on day 19, defective F1 male IgM titers remained depressed. These data demonstrate that an X-linked gene that affects B cell function influences malarial resistance in mice, presumably via a decreased specific IgM response, and the slow development of a specific IgG response to P. yoelii infection.     

Effect of immune heterozygous spleen cell transfer on resistance to mouse hepatitis virus infection in nude mice

The role of cell mediated immune response to mouse hepatitis virus (MHV) infection in mice was studied by transferring spleen cells from immune heterozygous littermates (nu/+). A suppressive effect on viral growth was seen in infected nude (nu/nu) mice, whereas immune nu/+ serum transfer had no effect. The protective effect of immune nu/+ spleen cells was significantly reduced by treatment with anti-theta serum plus complement but not with anti-Ig serum. In infected nu/nu mice which received transfers of immune nu/+ cells, neutralizing antibody appeared although the titer was not high enough to protect nu/nu mice from fatal infection. Histopathologically, lymphocyte infiltration in hepatic lesions was evident in infected nu/nu mice with nu/+ cell transfer, while it was slight without nu/+ cell transfer.