Activity Of Immune Spleen Cells Research Articles

Alteration of macrophage functions by cocaine.

Studies elucidating the effects of cocaine on immune cells and immune function are relatively recent. Although immunomodulation by cocaine has been reported by a number of investigators, it is not consistently associated with immunosuppression. A review sum­marized many of the earlier studies of cocaine on the immune system (1). Another study (2) describes a number of immune abnormalities in mice exposed to cocaine including an enhancement of neutrophil phagocytosis, a reduction of T-cell responses to the mitogen phytohemagglutinin, and cytotoxic activity of immune spleen cells. Other reports have described alteration of spleen cell subsets following injection with cocaine (3,4). A number of reports have described a reduction or alteration in the production of certain cytokines (5–7). In a series of publications, Peterson et al. (8–10) have reported an enhancement of HIV replication in cultures of human monocytes via the induction of transforming growth factor β (TGFβ) and tumor necrosis factor (TNFα). An increase in p24, one of the internal viral proteins, was used to quantify viral replication. A recent study (11) reported that Me culture supernatants from cells exposed to cocaine, modulate mesangial cell proliferation in vitro altering TGFβ, as well as IL-6.KeywordsPlaque SizeMouse Hepatitis VirusMesangial Cell ProliferationViral PlaqueReactive Nitrogen IntermediateThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The influence of cyclophosphamide on antitumor immunity in mice bearing late-stage tumors.

Spleen cells from mice bearing late-stage methylcholanthrene-induced tumor did not show any tumor activity when mixed with tumor cells in Winn's assay. Treatment of these mice with cyclophosphamide (CY) induced a tumor-inhibitory activity in spleen, occurring on day 7 after treatment, reaching its maximum on day 11 and disappearing by day 21. This antitumor activity could not be induced in control, tumor-free or T-deficient tumor-bearing mice. CY-induced tumor-inhibitory activity was immunologically specific, and mediated by Thy-1+, L3T4-, Ly-2+ cells. Contrary to spleen cells from untreated tumor-bearing mice, spleen cells from CY-treated tumor-bearing mice did not suppress the antitumor activity of immune spleen cells in Winn's assay. However, in contrast to immune spleen cells, CY-induced tumor-inhibitory cells did not manifest antitumor activity when transferred systemically (i.v.) into T-cell-deficient tumor-bearing mice. Even more, spleen cells from CY-pretreated mice, harvested 7-15 days after the drug administration, partially suppressed the antitumor activity of concomitantly transferred spleen cells from specifically immune mice. Nevertheless, CY-pretreated mice manifested concomitant immunity, i.e. these mice exhibited higher resistance to a second inoculum of the same tumor than did nontreated mice or even mice with excised primary tumor.

Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice.

Studies were performed to attempt to define the T cell subset responsible for resistance to Toxoplasma gondii. A temperature-sensitive mutant (ts-4) strain of T. gondii was used for immunization because it causes infection but does not persist in the host. Immunization with this strain induced marked resistance against lethal challenge infection with virulent strains of T. gondii in mice. The resistance could be transferred to normal recipient mice by i.v. injection of spleen cells from ts-4-immunized mice. Marked inhibition of cyst formation in the recipient mice was also noted. The protective activity of immune spleen cells was removed by pretreatment of the spleen cells with anti-Thy-1.2 and C, indicating that T cells are responsible for the observed protection. Pretreatment of immune spleen cells with anti-Lyt-2.2 and C completely ablated their protective effect; pretreatment with anti-Lyt-1.2 or anti-L3T4 and C had lesser effects on their ability to transfer resistance. The effect of anti-Lyt-1.2 was the same as that obtained with anti-L3T4. This suggested that one T cell subset that is partially responsible for protection has both Lyt-1.2 and L3T4 markers on the cell surface. These results indicate that there are substantial roles for both the Lyt-2+ and Lyt-1+, L3T4 T cell subsets in dual regulation of resistance against toxoplasma infection and that Lyt-2+ T cells are the principal mediator of the resistance.

Effector cells working for rejection of Ad12 tumors in mice.

Immune spleen cells (ISC) capable of inhibiting the growth of adenovirus type 12 (Ad12) tumors were raised in C57BL/6 mice by immunization with Ad12, fractionated according to their affinity for plastic and nylon-wool substrates or treated with various antisera plus complement, and subjected to the tumor-neutralization test (Winn) to define the effector cells for the cell species. Full antitumor activity of ISC was recovered in the cell fractions nonadherent to the two substrates; the antitumor activity of ISC was abrogated entirely by anti-Thy-1,2 serum and almost entirely by anti-Lyt-2.2 ascites fluid plus complement. These results clearly indicate that T-lymphocytes, particularly those bearing Lyt-2.2 antigen, are the principal effectors in ISC against Ad12 tumors in animals.

Transfer of immunity to Babesia microti of human origin using T lymphocytes in mice

Lymph node and spleen cells from mice infected with Babesia microti of human origin developed the ability to transfer adoptive immunity to naive mice within 25 days after infection. This protective activity was greater in cells obtained at 32 days than in cells obtained at 25 days postinfection and remained stable up to 52 days postinfection. Recipients of lymph node cells and spleen cells displayed similar peak parasitemias although 2 days after peak parasitemia, immune spleen cell recipients had significantly lower parasitemias than immune lymph node cell recipients. Strong protective activity was demonstrated when cells were transferred 1 day postinfection, while equal numbers of cells, transferred 3 days postinfection did not confer significant protection over nonimmune cells. There was also a suggestion that the number of immune spleen cells necessary for significant protection was directly related to the number of parasites inoculated. The subpopulation of lymphocytes responsible for the transfer of adoptive immunity to B. microti of human origin was then studied in BALB/c mice depleted of T lymphocytes by thymectomy and lethal irradiation. One day after infection with B. microti, T-cell-depleted mice were given complement-treated immune spleen cells, anti-θ serum-treated immune spleen cells, nonimmune spleen cells, or no cells. Similar experiments were performed comparing the effects of anti-immunoglobulin serum-treated and unfractionated immune spleen cells on B. microti parasitemia. Treatment with anti-θ serum abrogated the protective activity of immune spleen cells while anti-immunoglobulin serum treatment had no effect. These results suggest that immunologic memory of B. microti in BALB/c mice is modulated by T rather than B lymphocytes.

Cell-mediated immunity assayed by 51Cr release test in mice infected with mouse adenovirus

Immune spleen cells (ISC) from mice immunized with a sublethal dose of mouse adenovirus (M-Ad) were shown by the 51Cr release test to be cytotoxic to target mouse embryonic cells or lymphoid cells infected with M-Ad. The number of ISC required for release of statistically significant amounts of 51Cr from target cells varied from one sample to another, ranging from 5 to greater than or equal to 30 ISC per target cell. When 24-h-infected mouse embryonic cells were used as targets, the release of 51Cr became evident in 6 h after the addition of ISC to the cells, gradually increased with time, and then leveled off. Cytolytic activity of M-Ad ISC is specific for M-Ad, since ISC do not lyse mouse embryonic cells infected with human adenovirus type 12 and vice versa. Kinetic study of the development of cell-mediated immunity to M-Ad assayed by 51Cr release showed that cytolytic activity of ISC in infected mice became detectable 4 days postinfection, reached its peak level about 7 to 10 days postinfection, and fell to undetectable levels about 10 days thereafter. This is consistent with the data obtained by inhibition of intracellular viral antigen synthesis or by the macrophage migration inhibition test in our prevous reports.

Immunity to Plasmodium berghei in rats: reduced protective activity of immune spleen cells when transferred to recently infected rats

Immunity to Plasmodium berghei in rats: reduced protective activity of immune spleen cells when transferred to recently infected rats

Mechanism of induction of cell-mediated immunity to virus infections: in vitro inhibition of intracellular multiplication of mouse adenovirus by immune spleen cells

Mice were protected from lethal infection with mouse adenovirus (M-Ad) by adoptive transfer of immune spleen cells (ISC) that were prepared from mice immunized with M-Ad and not protected by sonicated ISC. However, a similar extent of protection was also observed by passive immunization with anti-M-Ad serum. In contrast, by in vitro experiments ISC were shown to be able to interrupt intracellular multiplication of M-Ad, whereas sonicated ISC, unimmunized mouse spleen cells, or anti-M-Ad serum were unable to do so. ISC were inhibitory in vitro when added within 12 h postinfection but not when added later. The inhibitory activity of ISC was regarded as due to cell killing by ISC, since the trypan blue exclusion test showed that above 80% of infected cells were killed by ISC even when 5'-fluorodeoxyuridine was added to the cells to block viral deoxyribonucleic acid synthesis, under which conditions control infected cells, to which ISC were not added or normal spleen cells were added, were kept alive at least for a few days. Kinetics studies in M-Ad-infected mice showed that the inhibitory activity of ISC became highest at 1 to 2 weeks postinfection and faded away thereafter in a few weeks, whereas serum antibody titer assayed by passive hemagglutination reached its peak level at about 4 weeks postinfection and declined gradually therafter.

Defects in cell‐mediated immunity during growth of a syngeneic simian virus‐induced tumor

Four assays of tumor-specific cell-mediated immunity were compared during growth of a syngeneic Simian-virus-40-induced tumor, mKSA. Major differences were found in immunity detected by the tumor neutralization test (the Winn test), direct tumor challenge, the microcytotoxicity assay and the -51chromium-release lymphocytotoxicity assay. Progressive growth of the neoplasm followed by loss of immunity (the eclipse phenomenon) was documented with the Winn test. It was established that this eclipse phenomenon represented a lesion in the T-cell system of tumor-bearing hosts. This lesion was found to be specific and unrelated to anatomic tumor location. The ability to produce graft-versus-host reactions, and the ability to respond to mitogens, were found to be generally intact in tumor-bearing animals. Cells capable of recognizing mKSA tumor antigens and reconstituting an immune response following surgical removal of tumor or upon transfer to normal mice were found in the spleens of mice bearing advanced tumors. No suppressor cells that might account for the eclipse phenomenon could be demonstrated. Tumor-bearer serum did not block neutralizing activity of immune spleen cells in the Winn test, and immune cells were capable of neutralizing tumor even in tumor-bearing hosts. The possibility that the lesion is intrinsic to T-cell precursors of effector cells is discussed.

Specificity and Development of Cytotoxic Thymus-Derived Lymphocytes in Lymphocytic Choriomeningitis

Abstract Cytotoxic capacity of immune CBA/H spleen cells for monolayers of L cells infected with lymphocytic choriomeningitis (LCM) virus is abrogated by prior incubation with AKR anti-ϑ ascitic fluid and complement, but is unaffected by treatment with anti-mouse-Ig serum and complement. Depletion of splenic macrophages, or addition of normal or activated (from listeria-immune mice) peritoneal macrophages, does not significantly modify the activity of immune spleen cells. Cell-mediated release of 51Cr from LCM-infected targets may thus be attributed to thymus-derived effector lymphocytes (T cells). Such T cells are specific insofar as they do not exhibit cytotoxic activity for monolayers infected with ectromelia virus, which are readily lysed by homologous immune cells. Development of cytotoxic lymphocytes is related to the dose of virus given: injection of high concentrations leads to peak activity on day 5. Maximal cytotoxicity is, however, mediated by spleen cells taken on day 7 from mice immunized with a relatively small dose of virus.

In Vitro Study of Antiviral Activity of Immune Spleen Cells in Experimental Venezuelan Equine Encephalomyelitis Infection in Mice

Abstract VEE-immune spleen cells from C57BL/6 mice exert a potent inhibitory effect on VEE viral growth in vitro when co-cultivated with infected L cell cultures. This inhibitory effect is both immunologically specific and dependent on time of spleen cell harvest after donor immunization with attenuated VEE virus. Neither interferon nor neutralizing antibody appear to be responsible for this specific antiviral activity. Studies with purified spleen or peritoneal cell populations demonstrate that only immune macrophages alone, or the combination of immune lymphocytes with normal macrophages, are active in inhibiting VEE-virus growth in cell culture. Finally, treatment of VEE-immune spleen cells with cytotoxic antisera directed at eliminating T cells removes the inhibitory effect on VEE replication in cell culture. Hence a two-cell system involving immunocompetent T cells and activated macrophages is proposed for the inhibition of VEE viral growth.

Mechanisms of recovery from a generalized viral infection: mousepox. II. Passive transfer of recovery mechanisms with immune lymphoid cells.

The following passive transfer experiments evaluated the contributions of the various host responses in recovery from mousepox. (a) Immune spleen cells transferred highly efficient antiviral activity, but preinfected recipients of these cells made no detectable splenic interferon or antibody in the 24 hr interval after cell transfer. (b) Passively administered interferon was ineffective. (c) Recipients of hyperimmune serum had much more antibody than recipients of immune spleen cells but significantly less antiviral activity. (d) Immune spleen cell populations with antiviral activity contained mediators of CMI to virus antigens. (e) The antiviral activity of immune spleen cells was specific; it was inhibited by in vitro treatment with ATS, anti-light chain serum, and anti-theta ascitic fluid, but not by removal of mononuclear phagocytes from the immune population. These results are interpreted to mean that recovery mechanisms conferred by immune spleen cells were triggered by specifically sensitized, thymus-derived lymphocytes, and that antibody and interferon responses were of less importance. A radiosensitive recipient component was necessary for the full expression of the antiviral activity of both immune cells and immune serum. It seemed likely that this component was the blood monocyte.

Immunity to malaria: III. Possible occurrence of a cell-mediated immunity to Plasmodium knowlesi in chronically infected and Freund's complete adjuvant-sensitized monkeys

Many of the monkeys sensitized with schizont-infected cells in Freund's complete adjuvant (FCA) survived challenge with homologous Plasmodium knowlesi. In view of the ability of FCA to promote induction of cell-mediated immunity, evidence was sought of delayed hypersensitivity and lymphocyte sensitization in monkeys which survived infection. The results of three groups of experiments are presented: (1) skin tests by intradermal injection of parasitized erythrocytes into chronically infected and FCA-immunized monkeys; (2) in vitro thymidine uptake (as a measure of DNA synthesis) by spleen and lymph node cells from sensitized and sensitized and challenged monkeys in the presence of specific and nonspecific antigens; and (3) measuring the release of 51Cr label from parasitized cells in the presence of immune and normal spleen cells. Examination of the intradermal injection sites revealed immediate reactions in both chronically infected monkeys and in monkeys sensitized with schizont-infected cells in Freund's adjuvant; in the former the immediate reaction increased with the duration of the infection. In the FCA-sensitized monkeys there was evidence of a delayed-type response. Both spleen and lymph node cells from FCA-sensitized monkeys were responsive in terms of increased DNA synthesis in vitro to the sensitizing antigen. This correlates with delayed hypersensitivity. No specific cytotoxic activity of immune spleen cells from FCA-sensitized or chronically infected monkeys on parasitized cells could be detected. A model system using sheep red cells gave positive results. Although these results suggest that in the FCA-sensitized monkeys there is a delayed hypersensitivity to malarial antigens, we do not know if this is involved in the protective mechanisms associated with sensitization with schizontinfected cells in Freund's complete adjuvant.