• Biomedical Science Letters
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• v.20 no.3
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• pp.147-155
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• 2014

It has well studied that immune cells are strongly related to tumor progression and tumor suppression. To identify the difference of immune cell between tumor bearing mice and normal mice, we examined systemically the immune cell of CT26 tumor bearing mice on 21 days after tumor cell administration. As previously reported, CD4+ and CD8+ T cells population of tumor bearing mice significantly decreased 38% and 30% on day 21 compared to that of normal mice, respectively. All subpopulation of CD4 and CD8+ T cell significantly decreased, except CD49b+ T cell subpopulation. But, myeloid cell population ($CD11b^{high}$ and all Gr-1+ subpopulation) of tumor bearing mice significantly increased on day 21. Especially, all subpopulation of CD11b+Gr-1+ cell of tumor bearing mice significantly increased on day 21. Also, Foxp3+$CD25^{high}$ CD4 T cell (regulatory T cells) population significantly increased on day 21. These results suggest that tumor can induce the decline of T lymphocyte and the expansion of myeloid cells and regulatory T cells, and provide the basic information for the study of tumor immunology.

• The Journal of Korean Medicine
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• v.24 no.1
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• pp.169-180
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• 2003

Background : Allergic asthma is thought to be mediated by $CD4^{+}$ T lymphocytes producing the Th2-associated cytokines. According to investigations of lung biopsies and respiratory secretions from patients, $CD4^{+}$ T cells and eosinophils are the main features of the inflammatory process. Object : This study aimed to find an inhibition effect on allergens induced by JCT (Jungchun-tang) and JCTG (Jungchuntanggagambang) through the change of $CD4^{+}$ T cells and $CD8^{+}$ T cells in BALF of rat, and to see the change of IgE m serum. Materials and Methods : Laboratory rats were primary sensitized with OA (ovalbumin); on day 1, rats of a control group and a sample group (SBP group) were systemically immunized by subcutaneous injection of 1mg OA and 300mg of A1(OH)3 in a total volume of 2 ml saline. The rats of the sample group were orally administered with an SBP water extract for 14 days after primary immunization. On day 14 after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2%(wt/vol) OA. A day after local immunization, BAL fluid and serum were collected from the rats. Total cells, lymphocytes, $CD4^{+}$ T cells, $CD8^{+}$ T cells, and $CD4^{+}$/$CD8^{+}$ ratio in the BALF, and IgE level in serum were measured and evaluated. Results : L Total cell in BALF of rat : JCT was observed to be significantly reduced but JCTG had no significant difference in comparison with the control group. 2. Lymphocytes in BALF of rat : JCT and JCTG were observed to be significantly reduced in comparison with the control group. 3. $CD4^{+}$T cells in BALF of rat : JCT was observed to be more significantly reducing than JCTG in comparison with the control group. 4. $CD8^{+}$T cells in BALF of rat : JCT and JCTG were observed not to be significantly different than in the control group. 5. $CD4^{+}/CD8^{+}$ ratio in BALF of rat : JCT and JCTG were observed not to be significantly different than in the control group. 6. The IgE level in serum : JCT and JCTG were observed to be significantly reduced in comparison with the control group. Conclusion : This study shows that JCT inhibits allergen-induced specially select $CD4^{+}$T cell channel in BALF of rat.

• Korean Journal of Pharmacognosy
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• v.29 no.2
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• pp.110-119
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• 1998

Sa-Mul-Tang(SMT) consist of Rehmanniae Radix Preparata, Paeoniae Radix Alba, Cnidii Rhizoma and Angelicae Gigantis Radix. In L1210 cells-transplanted BALB/c mice, T-lymphocyte apoptosis, $CD8^+T_C$ cells population in thymocyte and nitric oxide production in macrophage were enhanced, but phagocytic activity was decreased. SMT suppressed T-lymphocyte apoptosis and enhanced CD^4+T_H$ cells population, but did not affect nitric oxide production and phagocytic activity in L1210 cells-transplanted mice. In antitumor drugs-injected mice, T-lymphocyte apoptosis was enhanced, but $CD4^+T_H/CD8^+T_C$, cells population and T-lymphocyte proliferation were decreased. SMT suppressed T-lymphocyte apoptosis, and enhanced $CD8^+T_C$ cells population, T-lymphocyte proliferation and phagocytic activity in vincristine-injected mice. These results suggest that SMT enhances T cell-mediated immunity in L1210 cell-transplanted mice, and enhances T cell-mediated immunity and phagocytic activity in vincristine-injected mice.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Biomedical Science Letters
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• v.13 no.4
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• pp.325-332
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• 2007

Cell-mediated immune response (CMI) is a major immune protective mechanism against tuberculosis (TB) infection. Among several components involved in CMI, recent studies suggest that CD8+ T cells are important in controlling TB infection. In our previous report, we defined four Mycobacterium tuberculosis (MTB) derived epiotpe peptides specific for HLA-A*0201-restricted CD8+ T cells. These four peptides are $PstAl_{75-83}$, $ThyA_{30-38}$, $RpoB_{127-135}$ and $85B_{15-23}$. In this study, these epitope peptides specific CD8+ T cell responses in tuberculous pleurisy were investigated using ex vivo $IFN-\gamma$ elispot assay and intracellular $IFN-\gamma$ staining method. As a result, we observed these epitope peptide specific CD8+ T cell responses are induced in all three patients with tuberculous pleurisy suggesting that CD8+ T cells are involved in protective immune mechanism against MTB infection in tuberculous pleurisy. However, the CMI to mitogens and MTB antigens from pleural fluids of patients with tuberculous pleurisy does not seem to correlate with that from peripheral blood, although the sample size is too small to make any conclusion. In sum, the MHC I restricted CD8+ T cell responses seem to be induced efficiently in the pleural fluids, at the site of TB infection, in which the CMI is actively induced. In addition, these experiments suggest that MHC I restricted CD8+ T cell mediated immune responses are also involved in protective mechanism against MTB infection in extra-pulmonary TB.

• 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.

• Animal cells and systems
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• v.1 no.4
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• pp.657-663
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• 1997

The CD4 and CDS coreceptors, in conjunction with the T cell receptor (TCR) , make important contributions to the differentiation of thymocytes. They have been shown to be involved in the clonal deletion and positive selection processes during T cell development in thymus. To further analyze the role of CD4 and CDS proteins during T cell differentiation, we have generated transgenic mice constitutively expressing high levels of a native CD4 and a CD4{CDSa hybrid protein. The hybrid protein is composed of CD4 extracellular domain linked to the CD8a transmembrane region and cytoplasmic tail. The transgenes were driven by human beta-actin promoter, and therefore, they were expressed in all tissues examined including thymus, spleen, and lymph nodes. The resulting CD4 and CD4{CD8${\alpha}$transgenic mice were found to express the CD4 and CD4{CD8${\alpha}$ respectively, in developing thymocytes and peripheral T cells. The expression levels of transgenic proteins were 5-10 times higher than that of endogenous CD4 in thymus. However, total surface CD4 expression (CD4 or CD4{CD8${\alpha}$ transgenic protein plus endogenous CD4) of the transgenic mice were main. tained at similar levels compared to control littermates. Surface CD4 expression on CDS T cells, however, was significantly lower than that on cells expressing endogenous CD4. These results suggest that a total avidity between developing thymocytes and thymic stromal cells is impor. tant for differentiation of thymocytes.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• IMMUNE NETWORK
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• v.10 no.3
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• pp.104-108
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• 2010

CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress $CD4^+$ T cells, ameliorating autoimmune diseases, whereas it induces activation of $CD8^+$ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect $CD11b^+Gr-1^+$ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased $CD11b^+Gr-1^+$ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both $CD8^+$ T cells and $CD4^+$ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce $CD11b^+Gr-1^+$ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

• Molecules and Cells
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• v.39 no.7
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• pp.515-523
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• 2016

Long-term immunity to many viral and bacterial pathogens requires$ CD8^+$ memory T cell development, and the induction of long-lasting$ CD8^+$ memory T cells from a $na{\ddot{i}}ve$, undifferentiated state is a major goal of vaccine design. Formation of the memory$ CD8^+$ T cell compartment is highly dependent on the early activation cues received by $na{\ddot{i}ve}$ $CD8^+$ T cells during primary infection. This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs.