Transforming growth factor-beta 1 inhibits murine immediate and delayed type hypersensitivity.

Transforming growth factor beta 1 (TGF-beta 1) is a member of a gene superfamily that regulates growth, differentiation, and function of cells including several in vitro immune functions. Our study examined the systemic effect of TGF-beta 1 on murine delayed-type hypersensitivity (DTH), a model of T cell-mediated immunity that may depend on mast cells. Mice were immunized by i.v. injection of SRBC or by topical application of picryl chloride, and the responses were elicited by cutaneous challenge with the appropriate Ag. Systemic administration of TGF-beta 1 at the time of Ag challenge significantly reduced both the early and late phases of DTH. The effect of TGF-beta 1 on the release of serotonin from mouse peritoneal mast cells was examined. Results indicated that in vivo treatment with TGF-beta 1 24 h before mast cell harvest inhibited the in vitro release of serotonin in response to challenge with compound 48/80, or anti-IgE antibody. In contrast, treatment with TGF-beta 1 24 h before Ag challenge did not inhibit DTH indicating that mast cells may not be the direct target for TGF-beta 1 in the DTH models. In vivo treatment with TGF-beta 1 inhibited the IgE-mediated, mast cell-dependent, immediate hypersensitivity skin swelling response when injected at the time of, or 24 h before challenge. This suggests an effect on mast cells and a regulatory role for TGF-beta 1 in IgE-mediated responses.     

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.     

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.     

Systemic changes in hydrolytic enzyme activities in mice affected with murine leprosy

In order to investigate the behavior of hydrolytic enzymes in chronic infections, the activities of 17 hydrolytic enzymes were tested in limb muscles, heart muscle, spleen, liver, and kidney of lepromatous mice infected with Mycobacterium lepraemurium (M. lepraemurium) and their controls. Typical increases in those enzymatic activities were seen in spleen and liver, where pathological changes were the most pronounced, especially at the 11th week after the inoculation of the bacilli. At the 16th week, the enzymatic changes became less remarkable probably because of the decreased viability of tissues in these organs. The enzymatic changes observed could not be explained as due to bacterial enzymes. These findings are compatible with the notion that the increases in hydrolytic enzyme activities are related to tissue damage caused by murine leprosy.     

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).     

Systemic vascular reactivity during high-altitude pregnancy

There is an increased incidence of preeclampsia at high compared with low altitude. Increased vasoreactivity, possibly due to a deficiency of vasodilator prostaglandins, is thought to contribute to the etiology of preeclampsia. We sought to determine whether high-altitude exposure increased systemic vascular reactivity during pregnancy. We measured systemic vascular reactivity and contractile sensitivity of isolated aortic rings from pregnant and nonpregnant guinea pigs kept for 6 wk at either simulated high altitude (3,900 m) or low altitude (1,600 m). We found that pregnancy at high compared with low altitude increased baseline systemic vascular resistance (SVR) but not the SVR response to angiotensin II in awake unstressed guinea pigs. Contractile sensitivity to norepinephrine was also increased in aortic rings isolated from high-altitude compared with low-altitude pregnant animals. Meclofenamate, a prostaglandin synthesis inhibitor, did not equalize vasoreactivity in the high- and low-altitude pregnant guinea pigs or in their isolated aortic rings. We concluded that pregnancy at high compared with low altitude increased base-line SVR and aortic contractile sensitivity but that mechanisms other than decreased vasodilator prostaglandin production were responsible.     

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 by the H-2 gene complex of delayed type hypersensitivity

Identity at the major histocompatibility complex (MHC) was essential for successful transfer of delayed type hypersensitivity (DTH) in mice. The regions of the MHC involved differed according to the antigen used for sensitization. In the case of fowl gamma globulin (FGG), identity atI-A was necessary, whereas with dinitrofluorobenzene (DNFB), identity at theK, I, orD region was sufficient. These different genetic constraints probably reflect differences in the mechanisms by which antigens are presented to T lymphocytes. Cells from sensitized (CBA×C57BL)F₁ mice transferred DTH to FGG into parental-strain mice, but transfer was more effective in C57BL than in CBA with the same cell dose. This phenomenon is governed by the MHC, since there was better transfer intoH-2 ^b than intoH-2 ^k mice, regardless of their backgrounds. It may reflect the activity of an Ir gene-dependent process. Cells of one genotype (e.g., CBA), sensitized in chimeric mice derived from two MHC-incompatible strains (CBAC57BL), transferred DTH to both strains. These results do not support the notion that the genetic constraint observed in DTH transfer may be a result of the necessity for sensitized T and stimulator cells to match an identical MHC-coded cell interaction molecule. Rather, they favor the hypothesis that T cells recognize antigen, not as a naked determinant, but in close association with products of genes of the MHC.     

Intracisternal administration of Mycobacterium tuberculosis potentiates the delayed type hypersensitivity in guinea-pigs

The delayed type hypersensitivity (DTH) was studied in guinea-pigs using the skin test. The mycobacterium tuberculosis (M. tbc)--was applied by various routes. The control group received ovalbumin in Freund's incomplete adjuvant (FIA) into the footpad. The first experimental group received ovalbumin in Freund's complete adjuvant (FCA) into the footpad. The other experimental groups always received, in addition to ovalbumin plus FIA into the footpad, the M. tbc. 1. intracisternally, 2. intramuscularly, 3. intraperitoneally, 4. orally. On the day of administration of the sensibilizing substance, the body temperature was monitored. The skin test was measured after 14 and 21 days. It was established that, for the study of the DTH, the 21-day interval was more significant than the 14-day interval. A 100 times smaller dose of M. tbc. given intracisternally had the same immunostimulating effect as the injection of ovalbumin with M. tbc into the footpad (p less than 0.01). The size of the skin reaction was not only significantly influenced by the intramuscular and oral administration of M. tbc. On the other hand, the intraperitoneal administration inhibited the DTH (p less than 0.01). The increase of body temperature after the administration of M. tbc. correlated with the influence on the DTH except for the intraperitoneal administration. The route of the M. tbc. administration was crucial for the development of the DTH.     

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.     

Delayed hypersensitivity during casein-induced murine amyloidosis.

Cellular immunity has been studied in mice at various times during the induction of amyloidosis following multiple injections of casein. The assay system used was one which measured delayed hypersensitivity (DH) in vivo, by injecting antigen into the left ear lobe of sensitized mice, followed by the intravenous administration of ¹²⁵I-deoxyuridine (¹²⁵I-UdR). The ears were then cut off and the $\text{L}\text{R}$¹²⁵I-UdR ratio provided a measure of DH. It was found that DH to casein appeared in pre-amyloidotic mice, remained through the stages of mild and moderate amyloidosis and disappeared in severely amyloidotic mice. DH to fowl IgG disappeared after three injections of casein and remained absent at all times thereafter, likely due to antigenic competition. In contrast, DH to DNFB persisted at all times, even in the face of severe amyloidosis. These results have been interpreted to indicate that, using this assay, DH is normal during casein-induced murine amyloidosis.     

Primary antibody and delayed type hypersensitivity response of mice to ovalbumin

The control of the ability to respond to three doses of ovalbumin has been studied in an attempt to find the minimum dose of antigen necessary for activation of primary antibody response and delayed type hypersensitivity response. In seven of the ten mouse strains studied, concordance of the minimum dose needed to elicit the two responses was observed. Discordance is found in the other strains, suggesting that the ability to respond to ovalbumin is independently controlled in several cells. The antibody and delayed type hypersensitivity responses to ovalbumin are controlled by at least two genes, one localized in the major histocompatibility complex.