Kimifusa Mizunoe

Modulation of the antibody response to sheep erythrocytes in murine spleen cell cultures by a T cell mitogen extracted from Bordetella pertussis.

Mailard and Bloom have reported that the adjuvant effect of Bordetella pertussis vaccine (BPV) on antibody response in vitro to sheep erythrocytes (SRBC) was observed when BPV (5.1 •~ 105 to 6.4 •~ 106 organisms) and SRBC were added to cell cultures prepared from the spleen of BPV-primed mice, whereas this effect of BPV was not observed in cultures prepared from the spleen of normal mice (8). Recently, Murgo and Athanassiades showed that the adjuvant effect of BPV was observed on the antibody response in vitro to SRBC using spleen cells obtained from normal mice when large doses (1.0-1.5 •~ 108 organisms) of BPV had been added to the culture

Separation of an adjuvant-active glycolipid lacking peptide moiety from wax D preparation of mycobacterium tuberculosis strain aoyama B

Abstract A macromolecular and adjuvant-active glycolipid lacking the peptide part was separated from wax D preparation of M. tuberculosis strain Aoyama B by silica gel column and preparative thin-layer chromatographies. Although a glycolipid from wax D preparation of M. bovis BCG could also be separated by the same procedure, it was not adjuvant-active. Infrared spectra of both glycolipids were similar but not identical. The main absorptions showed the presence ofhydroxy, methylene and carbonyl groups, and absorption of primary amide and P-O groups in both spectra were very weak or slight. The nitrogen contents of both glycolipids were not detectable (below 0·01%). By alkaline hydrolysis, the glycolipid from M. tuberculosis was separated finally into the hydrophilic and hydrophobic parts forming intermediate products in the process. The molecular weight of the hydrophilic part was around 9300 daltons by gel filtration and it belonged to a fraction of lower molecular weight component(s) in the hydrophilic part of wax D preparation of M. tuberculosis strain H37Rv.

Mitogenic and adjuvant activities of polysaccharides from the cellular slime mold, Dictyostelium discoideum NC-4

Cell surface and extracellular polysaccharide fractions obtained from Dictyostelium discoideum NC-4 cultured in bacteria-free medium showed strong B-cell mitogenic activities. Upon periodate treatment of the extra-cellular polysaccharide fraction this activity completely disappeared. The extracellular polysaccharide fraction could also enhance the antibody response in vitro against sheep red blood cells.

Regulation of Anti-Hapten Antibody Response by Chemically Modified Carrier Antigen Preferentially Provoking Delayed-Type Hypersensitivity (DTH)

Experiments were carried out to determine whether or not the cell populations involved in DTH and in the suppression of antibody response are identical. The effects of four treatments, i.e., adult thymectomy (ATx), X‐irradiation, anti‐mouse thymocyte serum (ATS) and hydrocortisone (HC) on the induction of DTH and on the carrier‐specific suppression of antibody response were observed in mice immunized with chemically modified antigen, dodecanoyl‐BSA (d‐BSA), emulsified with complete Freunds adjuvant (CFA), with the following results: 1) DTH induced by immunization with D‐BSA remained constant in adult thymectomized mice, whereas the suppression of antibody response was not inducible in these animals. 2) Injection of low doses of ATS caused the depression of DTH in mice primed with D‐BSA, but did not affect the suppressive activities of their spleen cells. 3) Sublethal X‐irradiation 1 week prior to D‐BSA priming inhibited the generation of suppressor cells but did not affect the generation of cells mediating DTH. The suppressive effect was also abrogated by sublethal X‐irradiation given 2 days after immunization with DNP‐BSA (14 days after priming with D‐BSA). 4) The treatment of animals with HC 2 days before the footpad challenge or immunization with DNP‐BSA depressed the ability of animals to induce both DTH and the suppression of antibody response. However, the latter was more sensitive to HC than the former.

Activation of Distinct T Cell Subsets Involved in IgM Antibody Response of Mice by Pertussis Toxin from Bordetella pertussis Strain Maeno

T cell activation mechanisms in the spleen induced by pertussis toxin (PT) were investigated. The degree of T cell activation was judged from results of helper activity assessed by measuring the in vitro antitrinitrophenyl (TNP) IgM antibody response. When mice were injected intraperitoneally with 4 X 10(5) sheep erythrocytes (SRBC) and concomitantly given an intravenous injection with 10 micrograms of PT 4 days previously, significant generation of nonspecific helper T cells was observed unless primed T cells were stimulated in vitro with TNP-SRBC. Stimulation with TNP-SRBC resulted in marked suppression of helper activity because it induced generation of suppressor T cells specific for the carrier antigen.

Suppression of delayed type hypersensitivity induction to sheep red blood cells by concanavalin A in mice.

An examination was carried out on the in vivo effect of concanavalin A (Con A) on the induction of delayed-type hypersensitivity (DTH) to heterologous erythrocytes in mice. DTH induction was suppressed by an intravenous injection of 100 microng of Con A 1 day before, or simultaneously with immunization. This suppression was mediated by Con-A-activated spleen cells, and also by their cell-free extracts. However, this suppressive effect was abrogated by absorption of cell-free extracts with immunoadsorbent composed of rabbit anti-mouse thymocyte serum (ATS), indicating that suppressive factors for DTH induction make up one of the components extractable from Con-A-activated T cell population.

Immunostimulatory activity of 1-O-acylated muramyl dipeptides, with or without a 6-O-phosphoryl group, in aqueous form

Immunostimulatory effects of 1-O-acylated derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) methyl ester, with or without the 6-O-phosphoryl group, on augmentation of IgG antibody response against influenza hemagglutinin (HA) vaccine, in vivo macrophage activation and enhancement of non-specific host resistance against Pseudomonas aeruginosa infection were investigated. The activities were tested intraperitoneally (i.p.) in mice administered test samples solubilized or suspended in saline. The introduction of longer chain acyl groups into MDP methyl esters significantly induced enhancement of the IgG antibody response. Among them, the adjuvant activity of 1-O-linked 2-tetradecylhexadecanoyl (B30)-MDP methyl ester was comparable to that of 6-O-B30-MDP used as a positive control. Phosphorylation at the C6 position of the acylated MDP analogs did not induce a significant increment in the activity. With respect to phagocytic, cellular acid phosphatase and cytostasis-inducing activities, i.p. administration of acylated MDP analogs caused significant increment and activation of peritoneal macrophages. The cytostasis-inducing activity of 1-O-octadecanoyl- or 1-O-B30-MDP methyl ester with or without a phosphoryl group was more intensive than that of 6-O-B30-MDP. Acylated MDP analogs enhanced non-specific resistance against P. aeruginosa infection when the analogs were administered i.p. on the day before the infection. The enhancement was closely related to the accumulation of polymorphonuclear cells in the peritoneal cavity. The manifestation of these immunostimulatory activities by 1-O-acylated MDP analogs depended closely on the increasing carbon chain length of fatty acid substituents when administered in aqueous form.