• Title/Summary/Keyword: CD4 help

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The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer

  • Paytsar Topchyan;Siying Lin;Weiguo Cui
    • IMMUNE NETWORK
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    • v.23 no.5
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    • pp.41.1-41.21
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    • 2023
  • CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.

Requirement of CD4 Help for Induction of CD8 T Cell Response Specific for Virally Derived H60

  • Ryu, Su-Jeong;Kang, Bo-Ra;Kim, Seok-Ho;Kim, Tae-Woo;Chang, Jun;Choi, Eun-Young
    • IMMUNE NETWORK
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    • v.12 no.3
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    • pp.118-125
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    • 2012
  • CD40-CD40L-mediated help from CD4 T cells is essential to induce primary CD8 T cell responses specific to the non-inflammatory cell-based antigen H60. In this study, using H60 as a model antigen, we generated recombinant vaccinia viruses (rVVs) expressing the H60 CD8 epitope and investigated whether CD4 help was required to activate the CD8 T cell response specific to the virally expressed H60. The immune response after infection with rVVs expressing H60 was similar to that after immunization with H60 congenic splenocytes, with a peak frequency of H60-specific CD8 T cells detected in the blood on day 10 post-infection. A CD8 T cell response specific for virally derived H60 was not induced in CD4-depleted mice, but was in CD40-deficient mice. These results provide insights into the characterization of the CD8 T cell response specifically for antigens originating from cellular sources compared to viral sources.

Role for CD40 and CD40L Expression in Generating CD8 T Cell Response to Minor Histcompatibility Antigen, H60

  • Jung, Kyoung-Min;Choi, Eun-Young
    • IMMUNE NETWORK
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    • v.7 no.4
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    • pp.173-178
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    • 2007
  • Background: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. Methods: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. Results: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of $CD40^{+/+}$ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with $CD40^{+/+}$ CD4 T cells. Adoptive transfer of $CD40L^{+/+}$ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of $CD40L^{+/+}$ CD4 T cells was required even for memory CD8 T cells response to H60. Conclusion: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naive and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

Solubilization by $\beta$-Cyclodextrin: A Fluorescence Quenching Study

  • Panda, M.;Mishra, A.K.
    • Journal of Photoscience
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    • v.9 no.3
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    • pp.75-79
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    • 2002
  • Solubility of carbon tetrachloride ($CCl_4$) in water increases appreciably in presence of $\beta$-cyclodextrin ($\beta$CD). $CCl_4$ is a very good quencher of 1-naphthol (1ROH) fluorescence. By studying the quenching of fluorescence of 1ROH included in $\beta$CD cavity, it was found that there is an increase in the availability of $CCl_4$ around $\beta$CD in the aqueous medium. This could help to rationalize the enhanced solubility of $CCl_4$.

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The Identification of Proteins Interacting with CD1d (CD1d와 상호작용하는 단백질의 동정)

  • Hwang, Kwang-Woo;Chun, Tae-Hoon
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.263-267
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    • 2006
  • CD1d is an unique antigen presenting molecule which provides antigenic repertoires to NKT cells. To examine molecules required for CD1d antigen presentation, we determined an interaction between CD1d and several endoplasmic reticulum (ER) resident molecular chaperones by co-immunoprecipitation. Results indicated that calnexin and calreticulin seem to be bound to mouse CD1d, but TAP and tapasin do not bind. Further, we screened an yeat two hybrid system to identify proteins that help mouse CD1d transportation in the cytosol. We found that two proteins, heat shock protein a sub-unit $(Hsp90{\alpha})$ and protein kinase C and casein kinase substrate in neurons 3 (PACSIN-3), interact with CD1d. Future study will be focus on the role of these molecules during the CD1d antigen presentation.

Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

  • Du, Yong;Chen, Xin;Huang, Zhi-Ming;Ye, Xiao-Hua;Niu, Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3815-3819
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    • 2012
  • The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

Enhancement of Antigen-specific Antibody and $CD8^+$ T Cell Responses by Codelivery of IL-12-encapsulated Microspheres in Protein and Peptide Vaccination

  • Park, Su-Hyung;Chang, Jun;Yang, Se-Hwan;Kim, Hye-Ju;Kwak, Hyun-Hee;Kim, Byong-Moon;Lee, Sung-Hee;Sung, Young-Chul
    • IMMUNE NETWORK
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    • v.7 no.4
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    • pp.186-196
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    • 2007
  • Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.

Interleukin-10-Producing B Cells Help Suppress Ovariectomy-Mediated Osteoporosis

  • Yuhua Wang;Wei Zhang;Seong-Min Lim;Li Xu;Jun-O Jin
    • IMMUNE NETWORK
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    • v.20 no.6
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    • pp.50.1-50.11
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    • 2020
  • Osteoporosis is prevalent in elderly women and it may cause dental implant failure. In particular, estrogen deficiency in postmenopausal women leads to higher rates of osteoporosis prevalence. Immune cell-mediated effects involving the development of osteoporosis have been studied previously; however, the role of IL-10-producing regulatory B (B10) cells in osteoporosis is largely unclear. Here, we examined the role of B10 cells in osteoporosis. C57BL/6 mice were subjected to ovariectomy (OVX). Fifteen weeks after OVX surgery, the first molar of the right maxillary was extracted, and twenty-four weeks after OVX surgery, serous progression of osteoporosis was observed in the alveolar bone. Moreover, the proportion of CD19+CD5+CD1dhigh regulatory B cells, B10, and CD4+CD25+FoxP3+ regulatory T cells from the spleen of OVX mice decreased during the progression of osteoporosis, compared to controls. In contrast to regulatory cells, IL-17-producing Th (Th17) cell levels were increased in OVX mice. Adoptive transfer of B10 cells to OVX mice led to a decrease in Th17 cell abundance and inhibited the development of osteoporosis in the alveolar bone from OVX mice. Thus, our results suggest that B10 cells may help suppress osteoporosis development.

Evaluation on Immunopotentiation Activities of Combined Extract of Silkworm and Cinnamomum cassia in vivo (누에와 육계 복합 추출물의 in vivo 면역증진 기능성 연구)

  • Kim, Kyeong Jo;Park, Hae Jin;Kim, Il Gyu;Kim, Min Ju;Shin, Mi-Rae;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.33 no.4
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    • pp.19-26
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    • 2018
  • Objectives : The aim of this study was to investigate the immunopotentiating activity of combine extract that Silkworm and Cinnamomum cassia. Recently, acute epidemic diseases such as cold and viral respiratory diseases have been emerging. So, interested in immunity enhancement has been increasing, and research on natural products to promote immunity activity has been actively conducted. Methods : To confirm the immunopotentiating activity effect, Silkworm (SW), Cinnamomum cassia (CC), and SWCC combined extracts were treated 14 days at 300 mg/kg/day. The changes of glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT) in serum were analyzed after experiment. The changes in the total spleen cell number were measured. Immune cells in spleen were analyzed using fluorescence activated cell sorter (FACS). also, analyzed the expression of cytokines in spleen. Results : Total number of cells in the spleen and FACS analysis of T lymphocytes activated in the spleen showed that the SWCC combined treated group had much higher frequency of active cells than both single groups. The ratio of CD4+CD8+, CD4+CD69+ and CD4+CD25+ T cells in spleen, SWCC is higher than other groups except Nor in CD4+, CD4+CD69+, CD4+CD25+ T cells. The results of this study suggest that SWCC can help immune function via IL-2, IL-10, IL-12, IFN-${\gamma}$ cytokine production, increased T lymphocytes and splenocyte proliferation. Conclusion : Therefore, these results suggested that the SWCC combined extracts administration increase stronger immunity enhancement than when SW and CC adminstration.

Historical Control Data from 4-week Repeated Toxicity Studies in Crj:CD (SD) Rats

  • Lee, Jung-Min;Lee, Min-Ah;Do, Hyeon-Nam;Bae, Re-Ji-Na;Lee, Mi-Ju;Kim, Myoung-Jun;Jang, Ho-Song;Park, Sun-Hee;Lee, Hye-Yeong;Kang, Jin-Seok;Kang, Jong-Koo
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.268-275
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    • 2012
  • Reference ranges of standard experimental parameters are useful for comparisons in toxicology. The aim of this study was to collect data from 4-week repeated toxicity studies in Crl:CD (SD) rats, a strain widely used for toxicity and efficacy research, for establishing domestic reference values. Data on body weight, food consumption; urinalysis, hematological, and blood biochemical parameters; and organ weights were collected from 16 toxicity studies in 220 Crl:CD (SD) rats (110 males and 110 females). The studies had been performed at a single testing facility over the last 3 years and involved animals sourced from a single breeder. The findings were collated as means, standard deviations, percentages, and ranges. Urine volume, uterus weight, eosinophil, and basophil counts, and triglyceride, total bilirubin, and gammaglutamyl transpeptidase levels showed standard deviations of 30% or more. These historical control data would help to interpret the effects of test substances in routine toxicity and efficacy studies.