In vitro Primary Induction of T Cells Mediating Delayed Footpad Reaction and Acquired Cellular Resistance to Listeria monocytogenes

Mitsuyama, Masao; Handa, Toshiya; Koga, Tomohiro; Watanabe, Yoh-ichi; Yayama, T; Muramori, K; Nomoto, Kikuo

doi:10.1016/s0171-2985(88)80045-7

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…Negative selection revealed that Listeria-immune T cells of the L3T4+ Lytl+23phenotype produce lymphokines relevant to the expression of antibacterial immunity (16,17,19). Mitsuyama et al demonstrated that L3T4+ Lyt2-T cells generated in vitro were effective for expression of DTH and ACR (28). On the basis of these observations, the effector T cells obtained in our experiment had a surface phenotype of helper T cells.…”

Section: Discussionsupporting

confidence: 57%

Interleukin-1-induced promotion of T-cell differentiation in mice immunized with killed Listeria monocytogenes

et al. 1990

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We studied the effects of administration of recombinant interleukin-lao (rIL-la) to mice after immunization with killed Listeria monocytogenes cells on the promotion of the functional differentiation of T cells in vivo. Mice immunized with killed L. monocytogenes were unable to express cell-mediated immunity to specific antigen in vivo, as determined by delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR), and splenic T cells obtained from such mice were unable to respond to rIL-2 and specific antigen and to produce IL-2 after antigenic restimulation in vitro. When rIL-la was given to mice after immunization with killed bacteria, T cells became capable of responding to rIL-2 and specific antigen in vitro. These functions of T cells were similar to those from mice immunized with viable listeriae. Moreover, using a local passive transfer system, it was found that effector T cells mediating DTH but not ACR to L. monocytogenes were generated in mice treated with rIL-la after immunization with killed bacteria. These T cells were able to produce macrophage chemotactic factor but not macrophage-activating factor or gamma interferon in vitro in response to stimulation with specific antigen. These results suggest that in vivo administration of rIL-la facilitates the maturation of antigen-specific T cells mediating DTH and that different effector T cells mediating DTH or ACR are involved in cell-mediated immunity to L. monocytogenes. Protection against Listeria monocytogenes, a facultative intracellular bacterium, is mediated by cell-mediated immunity but not by humoral immunity (21, 27). Both acquired cellular resistance (ACR) and delayed-type hypersensitivity (DTH) are the manifestations of cell-mediated immunity raised against L. monocytogenes in animals (24, 25, 46). In mice, ACR against L. monocytogenes is usually measured by the capacity to eliminate challenge bacteria (23, 24, 46) and DTH is assayed by delayed footpad reaction (DFR) (25, 35). It is well-known that cell-mediated immunity, including DFR and ACR, can be induced in mice after immunization with viable L. monocytogenes but not with killed bacteria (2, 30, 31, 48). Killed bacteria are generally believed to be incapable of inducing specific cell-mediated immunity in mice. However, killed listeriae have been widely used as an effective stimulating antigen in the secondary stimulation of Listeria-specific effector T cells (6, 14, 17, 31). There is no convincing explanation as to why killed listeriae are unable to provoke DTH and ACR. Recently, we found that there was a significant difference in the ability to stimulate interleukin-1 (IL-1) production by macrophages between viable and killed cells of L. monocytogenes (29). IL-1, a cytokine produced primarily by cells of macrophage lineage, is believed to be essential in mediating several types of immune responses. In vitro, IL-1 enhances the activation and proliferation of T cells in response to mitogens (9, 37) or antigen (32). At least part of this effect may be attributed to the abilit...

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Section: Discussionsupporting

confidence: 57%

Interleukin-1-induced promotion of T-cell differentiation in mice immunized with killed Listeria monocytogenes

et al. 1990

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“…IL-12 is reported to induce NK cells to produce IFN-␥ alone (4, 7) or in combination with TNF␣ (43). Taking these findings into consideration, it is possible that macrophage-derived IL-12 plays a role in IFN-␥ induction in NK cells; however, some other macrophage-derived factor may be involved in our experimental model, since IL-12 is shown to be produced even after stimulation by non-LLO-producing strains (18,43) which are incapable of inducing specific protective immunity (25,28).…”

Section: Discussionmentioning

confidence: 99%

Induction of cytokine gene expression by listeriolysin O and roles of macrophages and NK cells

et al. 1996

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To determine the role of listeriolysin O (LLO) of Listeria monocytogenes in the host response at the initial stage of infection, cytokine gene expression in mouse peritoneal exudate macrophages and spleen cells was examined by reverse transcription-PCR. Expression of various cytokine mRNAs, especially those of interleukin-1 (IL-1), tumor necrosis factor alpha, gamma interferon (IFN-␥), and IL-12, was observed to occur in spleen cells after direct stimulation with an LLO preparation purified to a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Induction of mRNA expression by LLO was not blocked by cholesterol, which abrogated the hemolytic activity of LLO. After the depletion of NK cells in spleen cells by treatment with anti-asialo GM1 antibody plus complement, LLO-induced expression of IFN-␥ mRNA was decreased, indicating that NK cells were the main source of IFN-␥. After depletion of macrophages by passing spleen cells over a Sephadex G-10 column, expression of macrophage-derived cytokines, including IL-1␣, tumor necrosis factor alpha, and IL-12, was diminished. In addition, IFN-␥ mRNA expression was impaired, indicating that IFN-␥ mRNA expression from NK cells required signaling from macrophages. It is suggested that LLO is capable of inducing endogenous cytokines of mice, and both NK cells and macrophages are involved in the host cytokine response to LLO.

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“…The bacteria were grown in tryptic soy broth (Difco Laboratories, Detroit, Mich.) at 37°C for 16 h, washed repeatedly, suspended in phosphate-buffered saline (PBS), and stored at -70°C. Killed cells of L. monocytogenes were prepared by heating a viable bacterial suspension of a known concentration for 90 min at 74°C (25).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, when mice were immunized with killed cells of L. monocytogenes (22) or killed cells or lysates of Mycobacterium tuberculosis (33,34) along with an adjuvant, only DTH was expressed. Dissociated development of T cells mediating DTH (TDTH) and T cells mediating ACR (TACR) was also observed in an in vitro primary culture system inducing L. monocytogenes-specific T cells (25). Several reports showed that the effect of administration of anti-L3T4 monoclonal antibody to mice was different for DTH and ACR (5,24).…”

mentioning

confidence: 87%

Dissociated development of T cells mediating delayed-type hypersensitivity and protective T cells against Listeria monocytogenes and their functional difference in lymphokine production

et al. 1991

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CD4+ T cells mediating both delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR) were generated in mice after immunization with viable Listeria monocytogenes. In contrast, CD4+ T cells from mice immunized with killed L. monocytogenes in complete Freund's adjuvant were capable of mediating only DTH but not ACR. To determine the functional difference between T cells mediating DTH and T cells mediating ACR, we examined two different populations of T cells for profiles of lymphokine production after stimulation with a specific antigen in vitro. The production of interleukin-2 (IL-2) and IL-3 but not IL-4 was observed in both T cells mediating only DTH and those mediating DTH and ACR. In this respect, both types of T cells could be categorized into the TH1 population, and they produced macrophage chemotactic factor equally well. However, the production of gamma interferon (IFN-gamma) was observed only in T cells capable of mediating both DTH and ACR. This result was confirmed not only by an enzyme immunoassay specific for murine IFN-gamma but also by Northern (RNA) analysis for the detection of IFN-gamma mRNA. These results suggested that the TH1 population may be subdivided further into two distinct subsets and that the ineffectiveness of the killed bacterial vaccine may be partly explained by the dissociated development of T cell function.

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In vitro Primary Induction of T Cells Mediating Delayed Footpad Reaction and Acquired Cellular Resistance to Listeria monocytogenes

Cited by 9 publications

References 36 publications

Interleukin-1-induced promotion of T-cell differentiation in mice immunized with killed Listeria monocytogenes

Interleukin-1-induced promotion of T-cell differentiation in mice immunized with killed Listeria monocytogenes

Induction of cytokine gene expression by listeriolysin O and roles of macrophages and NK cells

Dissociated development of T cells mediating delayed-type hypersensitivity and protective T cells against Listeria monocytogenes and their functional difference in lymphokine production

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