Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)...Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].展开更多
AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treat...AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.展开更多
Objective:To investigate Phlebotomus(P.)sergenti Parrot,1917(Diptera:Psychodidae)salivary gland antigens and their immune response in human.Methods:Human volunteers were exposed to sand flies’bites in the laboratory,...Objective:To investigate Phlebotomus(P.)sergenti Parrot,1917(Diptera:Psychodidae)salivary gland antigens and their immune response in human.Methods:Human volunteers were exposed to sand flies’bites in the laboratory,and following each exposure the size of induration was recorded.The mean protein concentration of salivary gland lysate and specific anti-P.sergenti saliva IgG was measured.Sand fly salivary proteins were separated by SDS-PAGE and their immunoreactivity was examined by Western blotting assays.Results:Individuals exposed to P.sergenti salivary gland lysate for 8 months showed both antibody and delayed type hypersensitivity responses,although exposure for one month did not provoke any immune responses.The trend of antibody fluctuated during the exposure time and dropped by the end of antigen loading.The mean protein content was(0.36±0.08)μg in each pair salivary glands.Salivary gland lysate showed 11 to 12 major protein bands and 3 to 6 of them were immunoreactive.Conclusions:Our study showed that the salivary gland components of P.sergenti provoked both cellular and humoral immune responses in human.Furthermore,there are some immunogenic proteins in P.sergenti saliva which could be subjected for further investigation as vector-based vaccine candidate/s against anthroponotic cutaneous leishmaniasis.展开更多
Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response ...Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.展开更多
The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccina...The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.展开更多
It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as mo...It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.展开更多
We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune dis...We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune diseases,tumors,and infections as the cause of scleritis and suggested that the disease was caused by a local delayedtype hypersensitivity(DTH)induced by ocular trauma and was non-infectious.Still,the right epididymitis was infectious.Both conditions were treated successfully using steroids and antibiotics,respectively.Thus,early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.展开更多
Objective: To study the function in cellular immunity of patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-type hypersensitivity (DTH) to two recall a...Objective: To study the function in cellular immunity of patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-type hypersensitivity (DTH) to two recall antigens, tetanus toxoid (TT) and purified protein derivative(PPD), were measured in 5 patients with HIE and 15 healthy controls, respectively. Results: The CD4 + cell counts in HIE group were significantly lower than those in the control group (P<0.01). In contrast, CD8 + cells were significantly higher in HIE group than those in the controls. The induration sizes of DTH to two recall antigens were smaller in HIE group than those in controls (P<0.01). Conclusion: There is an immunologic dysfunction of T lymphocytes in the patients with HIE and T cells play an important role in the pathogenesis.展开更多
基金supported by the National Natural Science Foundation(81871691)the Beijing Municipal Natural Science Foundation(KZ202110025034).
文摘Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].
基金Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.
基金a part of project that was financially supported by School of Public Health,Tehran University of Medical sciences(TUMS),(Proj.No.95-02-27-31419)the center for research and training in skin diseases and leprosy.
文摘Objective:To investigate Phlebotomus(P.)sergenti Parrot,1917(Diptera:Psychodidae)salivary gland antigens and their immune response in human.Methods:Human volunteers were exposed to sand flies’bites in the laboratory,and following each exposure the size of induration was recorded.The mean protein concentration of salivary gland lysate and specific anti-P.sergenti saliva IgG was measured.Sand fly salivary proteins were separated by SDS-PAGE and their immunoreactivity was examined by Western blotting assays.Results:Individuals exposed to P.sergenti salivary gland lysate for 8 months showed both antibody and delayed type hypersensitivity responses,although exposure for one month did not provoke any immune responses.The trend of antibody fluctuated during the exposure time and dropped by the end of antigen loading.The mean protein content was(0.36±0.08)μg in each pair salivary glands.Salivary gland lysate showed 11 to 12 major protein bands and 3 to 6 of them were immunoreactive.Conclusions:Our study showed that the salivary gland components of P.sergenti provoked both cellular and humoral immune responses in human.Furthermore,there are some immunogenic proteins in P.sergenti saliva which could be subjected for further investigation as vector-based vaccine candidate/s against anthroponotic cutaneous leishmaniasis.
文摘Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.
文摘The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.
文摘It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.
基金Supported by Beijing Natural Science Foundation(7202229).
文摘We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune diseases,tumors,and infections as the cause of scleritis and suggested that the disease was caused by a local delayedtype hypersensitivity(DTH)induced by ocular trauma and was non-infectious.Still,the right epididymitis was infectious.Both conditions were treated successfully using steroids and antibiotics,respectively.Thus,early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.
文摘Objective: To study the function in cellular immunity of patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-type hypersensitivity (DTH) to two recall antigens, tetanus toxoid (TT) and purified protein derivative(PPD), were measured in 5 patients with HIE and 15 healthy controls, respectively. Results: The CD4 + cell counts in HIE group were significantly lower than those in the control group (P<0.01). In contrast, CD8 + cells were significantly higher in HIE group than those in the controls. The induration sizes of DTH to two recall antigens were smaller in HIE group than those in controls (P<0.01). Conclusion: There is an immunologic dysfunction of T lymphocytes in the patients with HIE and T cells play an important role in the pathogenesis.
