Regulation of antitubercular immunity in mice by genes of the H-2 complex

Development of DTH reaction and survival time after M. tuberculosis H37Rv infection have been studied in H-2 congenic and recombinant mice pretreated with high doses of BCG vaccine. In addition, in vitro proliferation of lymphocytes from infected CBA, B6 and 4R mice to PPD was studied in the presence of anti-I-A and anti-I-E mAbs. High doses of BCG vaccination (1 mg/mouse) have led to a significant inhibition of DTH and diminution of survival time in B10.M (H-2f) mice only, and to opposite effects in all other strains tested (H-2a, b, d, k, h4). In I-A+, I-E- 4R mice anti-I-Ak mAbs abrogated lymphocyte proliferation to PPD completely, while in I-A+, I-E- CBA mice only the mixture of anti-I-Ak and anti-I-Ek mAbs was effective.     

The mechanism of the delayed type of hypersensitivity

Кролики были ознак омл ены с БЦЖ вакцины, и посл е гиперчувств ительно сть кожи вак цины, и посл е гиперчу вствительно сть кожи дозе 5 μ (itg) очищ ен ного туберкулина (PT), веде нии внутривен но. Систе мные реакци и туберкули на hypersensitive от кроликов до 5 μ г PT состоит из лихор адка, и lymphopenia изменения в число гра нулоцитов (leucocytosis или leucopenia). Эта доза не производит т ем пературы или карт ина кр ови изменения в контро ля. Гиперчув ствительн ость был переведен пас сивно по клеток (200 до 500 млн.) hypersensitive от кроликов. Она прош ла успешно на использо вании клеток селезенки, перитонеального exudate (сол еных течение четырех ч асов или минеральное нефти в течение 48 часов) и белые клетки перифери ческой крови. В пассивн ом передача гиперчувс твительности в клетка х нормальных получате лей, все проявлений сист емных туберкулина Реа кция может быть вызвал, как в активном сенсибил изированная кроликов. Передача плазмы сенсиб илизированная кролик ов. Передача плазмы раз работка системного зад ерживается гиперчувс твительность в получат елями. Он сделал вывод о том, что результаты туб еркулина системные ре акции в первую очередь вызвала реакцию на hypersenstive клеток с туберкулина.     

The mechanism of the delayed type of hypersensitivity

1. (1)
   Простой метод демон страции цитостатиче ские воздействия раз бавленных туберкул ина и ПТ) на лейкоциты от hypersensitive кролики описана. О пределенный артикль Метод состоит в пятн а и мертвых живых кле ток (лейкоциты, мыть в четыре раза и приост ановлено в Tyrode раствор а) с 1% Конго красного и 0,2% после голубого Нила в течение четырех ча сов инкубации в vitro. Нес колько сто эксперим енты проводились и сто эксперименты пр оводились и гиперсс ылок чувствительно сти кроликов испыта ниям.     
   
   

The mechanism of the delayed type of hypersensitivity

Инкубационный пром ытого клетки hypersensitive кроли ков (лейкоциты, селез енки клеток, лимфоцит ов) в разбавленном туб еркулина в vitro приводит к появлению веществ с pyrogenic действий. Эти веще ств не фигурирует в к онтроля эксперимен тов, в которых клетки hypersensitive Были инкубировали без туберкулина или в которых клетки от н ормальных, не hypersensitive крол иков были инкубиров али.     

Regulation of the Drosophila engrailed gene by Polycomb repressor complex 2

Suppressor-of-zeste-12 (Su(z)12) is a core component of the Polycomb repressive complex 2 (PRC2), which has a methyltransferase activity directed towards lysine residues of histone 3. Mutations in Polycomb group (PcG) genes cause de-repression of homeotic genes and subsequent homeotic transformations. Another target for Polycomb silencing is the engrailed gene, which encodes a key regulator of segmentation in the early Drosophila embryo. In close proximity to the en gene is a Polycomb Response Element, but whether en is regulated by Su(z)12 is not known. In this report, we show that en is not de-repressed in Su(z)12 or Enhancer-of-zeste mutant clones in the anterior compartment of wing discs. Instead, we find that en expression is down-regulated in the posterior portion of wing discs, indicating that the PRC2 complex acts as an activator of en. Our results indicate that this is due to secondary effects, probably caused by ectopic expression of Ubx and Abd-B.     

Study on systemic reaction of delayed type hypersensitivity

Effectiveness of two different samples of PPD tuberculins was studied quantitatively. No differences were found in the effect on skin test in rabbits, extent of skin reaction in guinea pigs, edema of foot-pad in rats and inhibition of spleen cell migration in guinea pigs. Differences were observed in the systemic febrile reaction in rabbits and in examinations of the thickness of infiltrated skin in guinea pig tests. The results may serve as a basis for standardization of systemic reaction in rabbits.     

Study of systemic fever reaction of the delayed type hypersensitivity

The possibility of elaborating a model of fever reaction to a simple protein antigen, ovalbumin, was investigated. Administration of the antigen in adjuvants into the foot-pads or intravenously proved unsatisfactory and did not sensitize the animal to induction of a fever reaction to a challenging dose of antigen. Sensitization by the simultaneous intravenous administration of ovalbumin together with living BCG vaccine yielded positive results. The fever response to ovalbumin is specific, since rabbits sensitized with BCG vaccine only did not respond to the administration of ovalbumin. The degree of fever reactions to tuberculin and ovalbumin in the individual rabbits was more or less proportional. The given model is reproducible and is useful for experimental studies. Further experiments will be necessary, however, for detailed characterization and for analysis of the mechanism (antibody-mediated or delayed type hypersensitivity).     

Effect of the H-2 gene complex rates of fibroblast intercellular adhesion

The rate of collection of embryo fibroblast single cells by an embryo fibroblast monlayer was realted to the H-2 haplotype of the fibroblast monolayer. The rate was highest for the H-2s strains and lowest for the H-2k strains with all other strains examined being intermediate. As opposed to monolayers prepared from the A and C3H background animals, monolayers from B10 background mice only demonstrated an H-2 haplotype dependent rate differential after treatment with fetal calf serum or neuraminidase. The relationship that was seen between monolayer H-2 haplotype and rate of adhesion with embryonic monolayers was not observed with either congenic 3T3 cell lines or fibroblasts derived from adult tissues. It was further shown that the rate of single cell pick-up could be substantially reduced by incubating the monolayers with the appropriate polyspecific anti-H-2 antisera. The inhibition observed appeared to be directly related to anti-H-2 antibody binding and was not merely a function of ligand binding to the cell surface, as antisera directed against other fibroblast cell surface antigens did not significantly inhibit the adhesive rate. These results indicate a role for the H-2 gene complex in modulating fibroblast-fibroblast intercellular adhesion.     

Antigen-specific helper T cells recognize determinants encoded in the H-2D region of the H-2 gene complex

Observations have frequently been interpreted as showing that the helper T cells which collaborate with alloantigen-specific cytotoxic T-cell precursors can only recognize antigens encoded in the I region of the H-2 gene complex. An experimental system is described here that allows analysis of the recognition repertoire of these helper cells. CBA helper T-cell precursors can be primed in vitro to antigens encoded in the H-2 ^b gene complex. These helpers can then be tested for the existence of a subset of helper cells which recognize antigens encoded in the D region of H-2 ^b haplotype. CBA thymocytes were used as a source of cytotoxic T-cell precursors that respond poorly in the absence of exogeneous helper activity. The source of alloantigen was varied by using irradiated spleen cells from various (BALB/c × recombinant)F₁ hybrid mice as stimulator cells. When the stimulator cell bears BALB/c determinants recognized by the cytotoxic T-cell precursor and also bears only the D region antigens of the H-2 ^b haplotype, an anti-BALB/c cytotoxic response is generated only if the anti-H-2^b helper population contains cells able to recognize H-2D^b. A positive cytotoxic response was obtained, indicating that helper cells are not limited to recognition of I region antigens and can efficiently recognize antigens encoded in the D region of the H-2 gene complex. This was confirmed by the demonstration of helpers specific for H-2D^d. We were unable to detect any evidence for Ia-restricted recognition of the H-2D alloantigens, suggesting that, as for cytotoxic T lymphocytes (CTL), helper cell recognition of class I alloantigens is an unrestricted event.     

Specificity of suppressor cells of the delayed hypersensitivity type for Staphylococcus studied by immunoadsorption

The immunological specificity of T-suppressors obtained from mice after intravenous immunization with corpuscular antigen was shown. The splenocytes of such a mice suppressed DH to staphylococcal antigens, but not to sheep red blood cells. The suppressor cells under study were specifically adhesive to staphylococci.     

Effect of thyroid hormones on delayed type hypersensitivity reaction

The effect of long term administration of thyroid hormones and its deprivation on delayed type hypersensitivity (DTH) reaction to 2-4 dinitrochlorobenzene (DNCB) was studied. Animals were either pre-treated with thyroid hormones (T3 or T4) for 15 days and then subjected to DNCB skin test or the animals received thyroid hormones and simultaneously subjected to DNCB skin test. In both the cases DTH reaction was found to be increased significantly. When DNCB skin test was performed in the thyroidectomized animals, DNCB skin reaction was significantly decreased and the reaction was restored to normal following supplementation of thyroid hormones to the thyroidectomized animals. TLC and ALC were increased significantly following hormone treatment and thyroidectomized animals. TLC hand, induced significant depression in the count which was restored by hormone administration to the thyroidectomized animals.     

Regulation of the production of murine IgG2a by an H-2-linked gene and other unlinked genes

Alleles of at least two loci (rig-1 and Rig-2) regulate the levels of serum immunoglobulin of the Igh-1b class and allotype in BALB/c Ig^b (BAB/14) and (BALB/c × BAB/14)F₁ mice. The combined effect of the BALB/c alleles at these two loci is to lower Igh-1b levels significantly below those observed in other strains and below their own levels of Igh-1a in allotype heterozygous mice. The rig-1 locus is closely linked to or within the H-2 complex. Two alleles have been defined: rig-1 ^d and rig-1 ^b in H-2 ^d and H-2 ^b haplotypes, respectively. Homozygous rig-1 ^d d animals heterozygous for the BALB/c Rig-2 allele(s) have very low levels of Igh-1b. The designation of Rig-2 is provisional since it has not been mapped or defined as a single locus.     

Allergic encephalomyelitis: characterization of the determinants for delayed type hypersensitivity

Three non-encephalitogenic peptides derived from the encephalitogenic myelin basic protein of the central nervous system, produce delayed type hypersensitivity responses and elicit delayed skin reaction in guinea pigs sensitized with either peptide, the encephalitogenic tryptophan region (peptide E) or the basic protein. The amino acid sequence of the peptides is N-Acetyl-Ala-Ser-Ala-Gln-Lys-OH, forming the N-terminal region of the basic protein molecule, H-Gly-Ser-Leu-Pro-Gln-Lys-OH and H-Gly-Ala-Glu-Gly-Gln-Lys-OH representing residues number 69–74 and 117–122 of the basic protein respectively.     

Macrophage-T cell interactions involving Listeria monocytogenes--role of the H-2 gene complex.

This study reports on the in vitro interactions between T cells from Listeria-immunized mice, macrophages from normal mice, and heat-killed Listeria organisms. This interaction was assayed either by determing the amount of thymocyte mitogen in culture fluids after 24 hr, or by estimating the degree of T cell proliferation after 96 hr. Each assay depended on critical concentrations of macrophages, T cells, and heat-killed Listeria, points that were evaluated in a number of experiments. Both assays required specific Listeria-immune T cells. For an effective interaction, the T cells and the macrophages had to share the I-A region of the H-2 gene complex. Macrophages bearing Ia, which represented a minor population of macrophages, were essential for the proliferative response to macrophage-associated Listeria. Also, Ia-bearing macrophages were an important component in the interactions leading to increased secretion of mitogen. The immunogenic moiety associated with Listeria was short-lived, disappearing 24 hr after uptake of Listeria by macrophages. The interactions were not blocked by anti-Listeria antibodies but were partially sensitive to trypsinization.