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

The immune response of C57BL mice to a DBA/2 tumor allograft has been assessed in two assays of cell-mediated immunity, the in vitro lysis of 51Cr-labeled target cells and the antigen-mediated inhibition of macrophage migration. Both assays were shown to be measuring a T-cell-mediated reaction. Three types of experiments suggested that distinct subpopulations of T cells mediate these reactions. The tissue distributions of these activities was distinctive; both activities were present in spleens from i.p. immunized mice, but only macrophage migration inhibition activity was found in the peripheral lymph nodes (PLN) of such mice. Adoptive transfer of immune spleen cells into irradiated syngeneic recipients revealed that while a substantial amount of migration inhibition activity could subsequently be found in PLN, cytotoxic activity was found predominantly in the spleens of these adoptive hosts. Velocity sedimentation analysis of immune cells 14 days after i.p. immunization indicated that while the majority of cytotoxic activity was associated with small and medium lymphocytes, the majority of migration inhibition activity was associated with medium and large lymphocytes. In addition, normal spleen cells were fractionated by velocity sedimentation immediately before allosensitization in vitro. Subsequent analysis of the sensitized fractions revealed that the activity profiles for cytotoxicity and macrophage migration inhibition were not coincident. The implications of these observations are discussed.

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Antigen-specific suppressor T-cell activity in genetically restricted immune spleen cells.

Journal of Experimental Medicine ◽

10.1084/jem.148.5.1271 ◽

1978 ◽

Vol 148 (5) ◽

pp. 1271-1281 ◽

Cited By ~ 13

Author(s):

C W Pierce ◽

J A Kapp

Keyword(s):

T Cells ◽

T Cell ◽

Cell Activity ◽

Antibody Responses ◽

Spleen Cells ◽

Suppressor T Cells ◽

Specific Suppressor T Cells ◽

Immune Spleen Cells

Virgin spleen cells develop comparable primary antibody responses in vitro to syngeneic or allogeneic macrophages (Mphi) bearing the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), whereas immune spleen cells primed with syngeneic or allogeneic GAT-Mphi develop secondary responses preferentially when stimulated with GAT-Mphi syngeneic to the GAT-Mphi used for priming in vivo. These restrictions are mediated by products of the I-A subregion of the H-2 complex and are operative at the level of the GAT-Mphi-immune helper T-cell interactions. To investigate why these immune spleen cells fail to develop a significant antibody response to GAT-Mphi other than those used for in vivo immunization and determine the mechanism by which the restriction is maintained, spleen cells from virgin and syngeneic or allogeneic GAT-Mphi-primed mice were co-cultured in the presence of GAT-Mphi of various haplotypes. Antibody responses to GAT developed only in the presence of GAT-Mphi syngeneic to the Mphi used for in vivo priming; responses in cultures with GAT-Mphi allogeneic to the priming Mphi, whether these Mphi were syngeneic or allogeneic with respect to the responding spleen cells, were suppressed. The suppression was mediated by GAT-specific radiosensitive T cells. Thus, development of GAT-specific suppressor T cells appears to be a natural consequence of the immune response to GAT in responder as well as nonresponder mice. The implications of stimulation of genetically restricted immune helper T cells, and antigen-specific, but unrestricted, suppressor T cells after immunization with GAT-Mphi in vivo are discussed in the context of regulatory mechanisms in antibody responses.

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Modulation of Cell-Mediated Immunity by Lithium Chloride

Zeitschrift für Naturforschung C ◽

10.1515/znc-1994-9-1019 ◽

1994 ◽

Vol 49 (9-10) ◽

pp. 679-683 ◽

Cited By ~ 4

Author(s):

M. Kubera ◽

M. Bubak-Satora ◽

V. Holan ◽

W. Krol ◽

A. Basta-Kaim ◽

...

Keyword(s):

Lithium Chloride ◽

Nk Cell ◽

Graft Versus Host Reaction ◽

Cell Mediated Immunity ◽

Spleen Cells ◽

Host Reaction ◽

Graft Versus Host ◽

Control Value ◽

Licl Treatment

Abstract Immunomodulation of cell-mediated immunity was studied in mice treated with either lithium chloride (LiCl), anti-CD 8 monoclonal antibody or their combination. While 6-day LiCl treatment decreased the ability of their splenocytes to induce a local graft-versus-host reaction -anti-CD 8 abolished this effect. The proliferative response of spleen cells from those three groups of mice to concanavalin A stimulation in vitro was significantly increased. The natural killer (NK) cell toxicity of the mice was decreased by over 43% after the 6-day LiCl treatment, but was ×2.5 higher then the control value after a longer 21-d treatment. These results indicate that the immunomodulatory capacity of lithium is dependent on the type of cell population studied, and on the schedule of administration.

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Antigenicity of a Spontaneous Murine Mammary Adenocarcinoma during in Vitro Cultivation

Tumori Journal ◽

10.1177/030089167706300502 ◽

1977 ◽

Vol 63 (5) ◽

pp. 415-427 ◽

Cited By ~ 1

Author(s):

Anwar A. Hakim

Keyword(s):

Extracellular Protease ◽

Mammary Adenocarcinoma ◽

In Vitro Cultivation ◽

Membrane Glycoproteins ◽

Spleen Cells ◽

Alpha 1 Antitrypsin ◽

Immunogenic Properties ◽

Cells Cultured ◽

Immune Spleen Cells

The present study reports on the transplantability and immunogenic properties of a murine spontaneous mammary adenocarcinoma (AdCa) cultured under various conditions. When cultured under standard conditions for 300 days, AdCa cells became nononcogenic, and 74 % survived the effects of immune spleen cells. Cell cultures grown in presence of the « extracellular protease » retained their transplantability, and only 25 % survived the effects of immune spleen cells. In cotton-stoppered bottles without HEPES, the cells retained their transplantability and survived after incubation with immune spleen cells, whereas AdCa cells cultured in presence of human alpha-1-antitrypsin became less oncogenic and remained sensitive to the killing effects of immune spleen cells. When treated with serum of mice or rabbits immunized with AdCa cells, the cells cultured under standard conditions or grown in presence of the human antitrypsin became non-transplantable, whereas cells grown in cotton-stoppered glass bottles or in presence of the « extracellular protease » retained their oncogenicity. When cultured AdCa cells were incubated with cAMP and then used to immunize syngeneic hosts, tumors arising from a challenging dose of untreated AdCa cells grew faster in mice immunized with cAMP-treated cells than in mice immunized with untreated cells. On the other hand, immunization with AdCa cells treated with EDTA, iodoacetate, or heparin reduced the transplantability of the challenging AdCa cells. Treatment with vibrio cholera neuraminidase (VCN) at pH 5.6 increased the immunogenicity of AdCa cells: immunization with VCN-treated AdCa cells protected syngeneic hosts against challenge with untreated AdCa cells, whereas formalin-or glutaraldehydeflxed untreated AdCa cells gave a transient protection. Rabbit and mouse antisera raised against VCN-treated AdCa cells and against membrane glycoproteins of untreated AdCa cells showed definite though variable cytotoxic activity against cultured untreated AdCa cells.

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Cell-mediated immunity during the infection of CBA mice with Trypanosoma musculi

Canadian Journal of Microbiology ◽

10.1139/m74-016 ◽

1974 ◽

Vol 20 (1) ◽

pp. 105-106 ◽

Cited By ~ 6

Author(s):

Pierre Viens ◽

Pierre Pouliot ◽

G. A. T. Targett

Keyword(s):

Subcutaneous Administration ◽

Immune Serum ◽

Cell Mediated Immunity ◽

Spleen Cells ◽

Cba Mice ◽

Serum Transfer ◽

Immune Spleen Cells

CBA/J mice were infected with Trypanosoma musculi. On the 10th day of infection, when the parasitemia had become stabilized and parasites consisted only of adult (non-dividing) trypomastigotes, non-adherent spleen cells from immune donors were injected intravenously, with or without simultaneous subcutaneous administration of immune serum. The immune spleen cells accelerated the termination of infection whilst immune serum transfer had no effect on the course of the parasitemia.

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MECHANISMS OF RECOVERY FROM A GENERALIZED VIRAL INFECTION: MOUSEPOX

Journal of Experimental Medicine ◽

10.1084/jem.133.5.1074 ◽

1971 ◽

Vol 133 (5) ◽

pp. 1074-1089 ◽

Cited By ~ 90

Author(s):

R. V. Blanden

Keyword(s):

Antiviral Activity ◽

Immune Serum ◽

Mononuclear Phagocytes ◽

Host Responses ◽

Spleen Cells ◽

Hyperimmune Serum ◽

Recovery Mechanisms ◽

Interferon Responses ◽

Immune Spleen 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.

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H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. The H-2K structure involved is coded by a single cistron defined by H-2Kb mutant mice.

Journal of Experimental Medicine ◽

10.1084/jem.143.2.437 ◽

1976 ◽

Vol 143 (2) ◽

pp. 437-443 ◽

Cited By ~ 71

Author(s):

R M Zinkernagel

Keyword(s):

T Cells ◽

Cytotoxic T Cells ◽

Interaction Mechanism ◽

Lymphocytic Choriomeningitis ◽

Mutant Mice ◽

Target Cells ◽

Virus Infections ◽

Spleen Cells ◽

Immune Spleen Cells ◽

Critical Structure

Lymphocytic choriomeningitis or vaccinia virus-immune spleen cells of H-2 mutant mice carrying a point mutation in the K region (B6 H-2ba, B6 H-2bf) cannot lyse infected wild-type H-2Kb targets and vice versa. Yet, cytotoxic T cells specific for infected H-2Kba or H-2Kbf targets are generated during virus infections as shown by cold target competition experiments. The critical structure for the apparent restriction by the K or D regions of the H-2 gene complex of cytolytic interactions between T cells and virus-infected target cells are therefore each coded, at least as shown for the K region, by a single cistron. This finding is most readily accommodated within the altered self concept (postulating that T cells are specific for virus-modified self structures) but cannot exclude the possibility of a physiological interaction mechanism being responsible for the apparent H-2 restriction of virus-specific cytotoxic T cells.

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Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cell-mediated immunity in mice

Journal of General Virology ◽

10.1099/vir.0.037721-0 ◽

2012 ◽

Vol 93 (6) ◽

pp. 1204-1214 ◽

Cited By ~ 24

Author(s):

Lázaro Gil ◽

Lídice Bernardo ◽

Alequis Pavón ◽

Alienys Izquierdo ◽

Iris Valdés ◽

...

Keyword(s):

Capsid Protein ◽

Vaccine Candidate ◽

Cell Mediated Immunity ◽

Specific Cell ◽

Specific Response ◽

Spleen Cells ◽

Necrosis Factor Alpha ◽

Viral Challenge ◽

Tetravalent Vaccine

The interplay of different inflammatory cytokines induced during dengue virus infection plays a role in either protection or increased disease severity. In this sense, vaccine strategies incorporating whole virus are able to elicit both functional and pathological responses. Therefore, an ideal tetravalent vaccine candidate against dengue should be focused on serotype-specific sequences. In the present work, a new formulation of nucleocapsid-like particles (NLPs) obtained from the recombinant dengue-2 capsid protein was evaluated in mice to determine the level of protection against homologous and heterologous viral challenge and to measure the cytotoxicity and cytokine-secretion profiles induced upon heterologous viral stimulation. As a result, a significant protection rate was achieved after challenge with lethal dengue-2 virus, which was dependent on CD4+ and CD8+ cells. In turn, no protection was observed after heterologous challenge. In accordance, in vitro-stimulated spleen cells from mice immunized with NLPs from the four dengue serotypes showed a serotype-specific response of gamma interferon- and tumour necrosis factor alpha-secreting cells. A similar pattern was detected when spleen cells from dengue-immunized animals were stimulated with the capsid protein. Taking these data together, we can assert that NLPs constitute an attractive vaccine candidate against dengue. They induce a functional immune response mediated by CD4+ and CD8+ cells in mice, which is protective against viral challenge. In turn, they are potentially safe due to two important facts: induction of serotype specific cell-mediated immunity and lack of induction of antiviral antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.

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