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The cellular control of delayed hypersensitivity to Staphylococcus aureus in mice.

The cells which suppressed delayed hypersensitivity (DH) to Staphylococcus aureus in the mice were non-phagocytic, adhered to nylon wool and possessed surface immunoglobulin but no detectable Thy 1. antigen. They were probably B lymphocytes and the suppression which they mediated appeared to be specific. The mature suppressor cells were radiosensitive. Their precursors were sensitive to large doses of cyclophosphamide. Suppressor-cell activity in the spleen reached a peak after two subcutaneous S. aureus infections and declined thereafter. This decline might be related to the appearance of DH to S. aureus in mice after four or more staphylococcal infections.

Animals↗

[Protective role of effectors and T-suppressors of delayed hypersensitivity in mice with a localized staphylococcal infection].

To induce delayed hypersensitivity (DH) in mice, experimental local infection with a small dose of Staphylococcus aureus was used. The production of suppressor cells was shown to occur after the intravenous injection of a large dose of killed staphylococcal culture. Experiments with the use of cell transfer and the treatment of lymphocytes with Thy-1 antiserum in the presence of the complement demonstrated the T-lymphocytic nature of DH and its suppression. The study revealed that the role played by DH in antistaphylococcal immunity was different in the animals infected by the subcutaneous routes; besides, the regulatory action of T-suppressors of DH was established.

Animals↗

Delayed hypersensitivity in the mouse induced by hapten-carrier complexes.

Delayed hypersensitivity (DH) in the mouse was studied with complexes of dinitrophenyl (DHP) as hapten and bovine serum albumin (BSA), mouse immunoglobulin (MIg) and polyvinylpyrrolidone (PVP) as carrier. Priming with BSA induced strong DH against this carrier, but DN of decreasing strength against complexes with increasing DNP:carrier ratio. Priming with DNP-BSA complexes never resulted in a DH against BSA or DNP 3-minusBSA. Injections of DNP 16-minusBSA and DNP 28-minusBSA induced positive DH which increased with the hapten:carrier ratio of the eliciting antigen. The complexes with an isologous carrier DNP 48-minusMIg or DNP 90-minusMIg induced positive reactions against both complexes but not against the weakly substituted DNP 11-minusMIg. The latter only primed for itself. The importance of the DNP groups as determinant in these DH reactions is stressed by the cross-reactions between DNP-BSA and DNP-MIg complexes and by the induction by DNP 16-minusPVP of positive DH against DNP 28-minusBSA. Cyclophosphamide (Cy) treatment before priming with complexes induced enhanced DH against complexes with sufficient hapten:carrier ratio. Priming with carrier under Cy treatment induced no DH against complexes. All these results indicate that carrier determinants are not involved in the DH against complexes. After priming wtih complexes with a low hapten:carrier ratio the DH is directed against new antigenic determinants (NAD) groups. After priming with complexes with high ratios DH is directed against DNP groups. With adoptive local transfer of spleen cells of primed animals and pretreatment of these cells with anti-thymocyte serum or anti-plasma cell serum and complement it was possible to demonstrate that the T cell was responsible for the DH reactions. The involvement of different determinant groups on the hapten-carrier complexes in immune reactions is discussed.

Animals↗

[Delayed hypersensitivity to the surface antigen of the hepatitis B virus].

Delayed hypersensitivity to HBsAg in patients with viral hepatitis, chronic liver diseases and in healthy persons was determined in the leukocyte migration inhibition test in agar. Most of the patients with viral hepatitis B (61.7%) at the acute stage showed hypersensitivity to HBsAg. This hypersensitivity appeared not earlier than during the second or third decade of the disease. The positive results of the leukocyte migration inhibition test in some patients with chronic liver diseases indicated that these diseases were probably etiologically linked with hepatitis B virus. The use of the leukocyte migration inhibition test with HBsAg for the diagnosis of viral hepatitis B is proposed.

Cell Migration Inhibition↗

Antitumor immunity after surgical removal of 3-methylcholanthrene-induced murine tumors: correlation between resistance and delayed hypersensitivity reaction.

The relationship between tumor resistance and the antitumor delayed hypersensitivity reaction (TDHR) after resection of the tumor was studied by using the syngeneic 3-methylcholanthrene-induced murine tumor, MCA-DDD. MCA-DDD was inoculated subcutaneously into the tail of DDD mice and 4 weeks later the tumor-bearing tail was resected. The tumor resistances of the mice were then determined from the diameters of the tumor that developed 14 days after subcutaneous challenge of the mice with tumor cells in the flank. It was found that the mice showed a specific resistance to the tumor until 30 days after tumor resection. In parallel with tests on tumor resistance, TDHR of the mice after tumor resection was examined by the footpad test. The cell-free fraction of sonicated MCA-DDD tumor cells was used as the preparation of tumor antigens. TDHR of the mice appeared soon after tumor resection, reached a maximum on day 7, and then decreased slowly until day 29. Mice that acquired tumor resistance showed rapid increase of TDHR after challenge with fresh tumor cells. TDHR was high on day 4 after the challenge and its level was well correlated with tumor resistance of the mice.

Animals↗

Effects of hyaluronan on models of immediate and delayed hypersensitivity in the rat.

Others have previously shown that superoxide dismutase conjugated with hyaluronan (HA) retains enzymic activity but is non-immunogenic. Whether HA could be widely used to prevent sensitisation to protein/polypeptide therapeutics is not known. In this study we investigated the effects of HA on bovine serum albumin (BSA) and methylated BSA pleural reactions in sensitised rats (active Arthus and delayed hypersensitivity reactions respectively) and on a reverse passive Arthus reaction in which rats received an intravenous injection of rabbit immunoglobulin and intrapleural challenge with goat anti rabbit immunoglobulin. HA suppressed the active Arthus and delayed hypersensitivity models when administered at the time of sensitisation but only the delayed hypersensitivity model at the time of intrapleural challenge. HA did not modulate the reverse passive Arthus reaction. The results show no evidence that simple mixing of HA with antigens masks antigenic determinants. However, HA appeared to have suppressive effects on both antibody and cell-mediated immune reactions. Therefore it may not be necessary to conjugate protein/polypeptide therapeutics to HA in order to prevent immune sensitisation.

Animals↗

[Effect of schizophyllan on delayed hypersensitivity in the mouse (author's transl)].

The delayed cutaneous hypersensitivity test with picryl chloride was used to demonstrate the effect of sonicated schizophyllan (SPG-S) on cellular immunity in mice. The increase of ear thickness in mice treated with SPG-S (0.5 approximately 10.0 mg/kg) 24 hours before the sensitization with picryl chloride proved to be significantly larger than that in untreated mice on testing with picryl chloride at 7 days following sensitization. Mice were intramuscularly injected with SPG-S (5.0 mg/kg) on -48, -24, 0, +24 or +48 hours of sensitization. Remarkable stimulating effect of SPG-S on the delayed hypersensitivity was recognized in all groups of mice, being somewhat lower in the group treated with SPG-S 48 hours after the sensitization. Stimulating effects of lipopolysaccharide, concanavalin A, pokeweed mitogen and SPG-S on the delayed hypersensitivity were compared. The effect of SPG-S was similar to that of concanavalin A, a nonspecific stimulant for T cells.

Animals↗

Inhibition of delayed hypersensitivity reactions by a new agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10).

A newly synthesized compound, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10), has been reported as an inhibitor of delayed hypersensitivity reaction. In the present paper, the mechanisms regarding the inhibitory action of IG-10 was investigated on delayed hypersensitivity reactions. p-Phenylenediamine-induced contact dermatitis in guinea pigs was significantly inhibited when the drug was given in a dose of 100 mg/kg p.o. at various times after challenge with the antigen. IG-10 inhibited both contact dermatitis and monocytes or neutrophils infiltrations induced by picryl chloride in mice. A skin reaction, similar to that seen in the case of delayed hypersensitivity reaction, was induced by an intradermal injection of phytohemagglutinin-P (PHA-P) stimulated lymphocytes in guinea pigs. This reaction was a useful method for assessing the effect of drugs on the release of lymphokines, particularly skin reactive factor (SRF). IG-10 in a concentration of 10(-5) g/ml inhibited the release of SRF as well as the release of migration inhibitory factor (MIF) from guinea pig lymphocytes stimulated by PHA-P. The reduction of delta 4-3-ketone of aldosterone and/or hydrocortisone by rat liver homogenates was not affected with IG-10, unlike that seen in the case of glycyrrhizin.

Aldosterone↗

Mechanisms in the suppression of delayed hypersensitivity in the guinea pig by 6-mercaptopurine. II: Kinetic and morphologic studies on the monocyte-macrophage component.

The effect of 6-mercaptopurine on the development and expression of delayed hypersensitivity was studied in the guinea pig. Results indicated that 6-MP produced its suppressive effects primarily by action on cells of the monocyte-macrophage series. Suppression could occur under conditions of both developing and pre-established delayed hypersensitivity. The defect primarily involved newly synthesized, bone marrow-derived monocytes. Marked alterations in monocyte macrophage generation and distribution, especially the T1/2 of circulating monocytes were demonstrated. Suppressive effects were associated with the appearance of a unique morphologic microscopy. Finally, the in vivo expression of delayed hypersensitivity correlated better with a variety of parameters relating to qualitative macrophage function and distribution rather than those relating to quantitative macrophage levels.

Animals↗

Neutrophil function, serum opsonic activity, and delayed hypersensitivity in surgical patients.

The phagocytic function (e.g., phagocytosis, chemiluminescence, and chemotaxis) of polymorphonuclear leukocytes (PMNs), delayed hypersensitivity, and serum opsonic capacity were studied in 29 patients who underwent major surgical procedures, primarily abdominal surgery. The phagocytic capacity and chemiluminescence were normal in all patients as compared with healthy donors, and no difference in phagocytosis was found before or after operation. However, PMNs of 14 patients (48%) showed diminished chemotactic activity after surgery, but the influence of surgery on chemotaxis could not be demonstrated. About 30% of the patients had depressed delayed hypersensitivity after operation, as measured by skin testing using three recall antigens. The mean induration of the skin tests was 6.9 +/- 3.4 mm before operation and 3.6 +/- 2.9 mm thereafter (P = 0.006). The opsonic capacity of patient sera was measured as uptake by normal donor PMNs of staphylococci opsonized in patient serum. Eleven of 19 preoperative serum samples had an opsonic capacity comparable to that of normal control sera; the opsonic capacity of postoperative serum samples of the same patients was significantly decreased as compared with preoperative values. In seven patients the opsonic capacity of postoperative serum samples correlated with decreased levels of IgG in the sera but not with complement activity.

Adult↗

Relationship of BCG-induced pulmonary delayed hypersensitivity to accelerated granuloma formation in rabbit lungs: effect of cortisone acetate.

The role of local pulmonary delayed hypersensitivity in accelerated pulmonary granuloma formation was investigated using cortisone acetate, an immunosuppressive drug that appears to preferentially eliminate committed lymphocytes at appropriate doses. Data are presented showing that cortisone acetate suppressed local pulmonary delayed hypersensitivity at the time of and subsequent to challenge with BCG. Furthermore, cortisone damage appeared to involve primarily committed lymphocyte populations since the defect was repairable with sensitized spleen cells, an unlikely source of macrophage precursors.

Animals↗

Thalidomide as "salvage" therapy for patients with delayed hypersensitivity response to infliximab: a case series.

Infliximab is efficacious for refractory Crohn's disease, but delayed hypersensitivity reactions preclude retreatment for patients experiencing this complication. We report the results of four patients offered enrollment in an open label trial of thalidomide as "salvage" therapy for their refractory disease. Two patients with active fistulous disease and two with lumenal disease received open-label thalidomide 200 mg every night and were evaluated monthly at the University of Chicago Clinical Research Center for 12 weeks. Before administration, patients signed an informed consent form discussing the potential risks of thalidomide use. Female patients of child-bearing age underwent serum pregnancy testing every 4 weeks. Response was defined as an absolute decrease in Crohn's Disease Activity Index (CDAI) by 100 points or improvement in two of three clinical parameters for fistulous disease. A patient with a single perirectal fistula had complete closure by 4 weeks, the other had noticeable improvement of five perianal fistulae at 4 weeks and complete closure by 12 weeks. One lumenal patient had a CDAI decrease of 250 points in 4 weeks. The fourth patient withdrew secondary to sedation after only a week of therapy. Two patients (one fistula, one lumenal) continued thalidomide past the 3-month study period and remained in remission at 5 and 7 months. Side effects reported were sedation (four of four patients), hypertension (one of four), and peripheral neuropathy (one of four). Thalidomide appears to be a safe and effective alternative for short-term healing in patients who develop infliximab-induced delayed hypersensitivity reaction and may be an alternative strategy for those at risk.

Adult↗