• 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.

• Biomedical Science Letters
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• v.1 no.1
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• pp.27-35
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• 1995

Several studies showed that the immunological factors such as CD4+ cell number, CD4%, CD8+ cell number and CD4/CD8 ratio and the serological factors such as, ${\beta}^2$-microglobulin(${\beta}^2$-MG), neopterin, soluble CD4, and soluble CD8 are related to the risk of development of AIDS. Especially, the CD4+ cell counts have been used to monitor progresson of HIV disease, to stratify, and to follow patients in clinical trials. Recently, the Centers for Disease Control and Prevention(CDCP) in USA has made the CD4+ cell count as a part of the classification of HIV disease. It is composed of 3 categories such as 1, 2, and 3 which asr $\geq$ 500/$mm^3$, 200/$mm^{3} $\geq$ and < 500/$mm^3$, and < 200/$mm^3$, respectively. In this study, to estimate the differences of immunological factors between HIV-infected and normal human groups in Korea, CD4+ T and CD8+ T cells, and the CD4/CD8 ratio were measured in 185 HIV-infected subjects and 140 healthy adult subjects. The lymphocyte subsets such as CD4+ T and CD8+ T were analysed by flow cytometer(FACStar) with two-color immunofluorescent stain using monoclonal antibodies such as anti-CD4 and anti-CD8 antibodies. The absolute numbers and percentages of CD4+ T and CD8+ T and the CD4/CD8 ratio of HIV infected persons were $462\pm{277}/mm^3$, $18.2\pm7.7%$, $1,170\pm{534}/mm^3$, $47.0\pm10.6%$ and $0,43\pm0.26 whereas those of uninfected persons were $886\pm{299}mm^3$, $32.9\pm{7.0%}, 730{\pm}259/mm^3$, $26.8\pm6.4%$ and $1.31\pm0.46$(P<0.01). In addition, estimating the reference values of peripheral blood lymphocyte subsets of Korean, the absolute numbers and percentages of CD4+ T and CD8+ T and the CD4/CD8 ratio of 140 healthy adults persons were measured and compared with those of foreigners. The reference ranges of CD4+ T cells, CD8+ T cells, CD4％, CD8%, and the CD4/CD8 ratio and 1.31$\pm$0.46, respectively. The significant differences were not observed when compared with those of foreigners. However a little difference was observed in the percentages of CD4+ T and the absolute numbers of CD8+ T between the normal values of Korean and those of foreigners were $43.6\pm8.9%$, $560\pm{230}/mm^3$. This result can also be useful as a basic data for the treatment and surveillance of HIV-infected patients in Korea.

• Animal cells and systems
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• v.3 no.3
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• pp.331-336
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• 1999

p56$^{Ick}$, a cytoplasmic protein tyrosine kinase of the src family, is non-covalently associated with the cell surface coreceptors CD4 and CD8, which are expressed on thymocytes and mature T cells. The coreceptor protein plays an important role during the differentiation of thymocytes and the activation of T cells. DNA constructs were designed to study the roles of CD4 and CD8 during the differentiation of thymocytes. One is a chimeric cDNA which consists of coding regions for the extracellular domain of CD8a and the transmembrane and cytoplasmic domain of CD4. The other is the same chimeric cDNA but with a point mutation converting Cys to Ala in the Ick-binding site to disrupt the association. We confirmed that the CD8a/CD4 chimeric molecule bound to Ick more efficiently than the wild type CD8a protein. However, the chimeric protein with the Cys$leftrightarro$Ala mutation did not associate with Ick. The results suggest a possibility that the CD8a/CD4 chimeric protein may behave like a CD4 protein in associating with Ick and that it may deliver a signal inside the cell in a similar manner, Analysing effects of the mutant CD8a/CD4 chimeric protein expression in developing thymocytes will elucidate the role of Ick during the determination of CD4/CD8 cell lineages.

• 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.

• BMB Reports
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• v.49 no.1
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• pp.11-17
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• 2016

The gastrointestinal tract forms the largest surface in our body with constantly being exposed to various antigens, which provides unique microenvironment for the immune system in the intestine. Accordingly, the gut epithelium harbors the most T lymphocytes in the body as intraepithelial lymphocytes (IELs), which are phenotypically and functionally heterogeneous populations, distinct from the conventional mature T cells in the periphery. IELs arise either from pre-committed thymic precursors (natural IELs) or from conventional CD4 or CD8αβ T cells in response to peripheral antigens (induced IELs), both of which commonly express CD8α homodimers (CD8αα). Although lineage commitment to either conventional CD4 T helper (Th) or cytotoxic CD8αβ T cells as well as their respective co-receptor expression are mutually exclusive and irreversible process, CD4 T cells can be redirected to the CD8 IELs with high cytolytic activity upon migration to the gut epithelium. Recent reports show that master transcription factors for CD4 and CD8 T cells, ThPOK (Th-inducing BTB/POZ-Kruppel-like factor) and Runx3 (Runt related transcription factor 3), respectively, are the key regulators for re-programming of CD4 T cells to CD8 lineage in the intestinal epithelium. This review will focus on the unique differentiation process of IELs, particularly lineage re-commitment of CD4 IELs. [BMB Reports 2016; 49(1): 11-17]

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.438-443
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• 2007

The purpose of this research is to examine the effects of Kamijihwang-tang(KJHT) on CD+4 T cells and CD8+ T cell ovalbumin (OVA)-induced asthmatic mice. C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four a week) for asthma induction. Two experimental groups were treated with different concentrations of KJHT (400 mg/kg and 200 mg/kg) extract and cyclosporine A (10 mg/kg) for the later 8 weeks. At the end of the experiment, the mice lung, peripheral lymph node (PLN), and spleen were removed and CD4+ T cells and CD8 + T cells for analyzed by flow cytometer. Number of CD4+ T cells in lung, PLN, spleen of the KJHT group (400 mg/kg) were significantly decreased compared with that of control group. Number of CD8+ T cells in lung, PLN, spleen of the KJHT group (200 mg/kg) were significantly decreased compared with that of control group. The results of this study suggest that KJHT alleviated asthmatic hyperactivity through CD4+ and CD8+ T cells. Further study of relative cytokines is expected.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.117-128
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• 2004

Objectives : To examine the effects of Gojineumja on white rats which deteriorated immunity caused by Methotrexate(MTX), first of all, MTX was fed to the rats once a day for 4 day. Methods : After the immune response of the rats are deteriorated, dried extracts of Gojineumja(GJE) mixed in water was fed to the white rats once a day for l4days. The next conclusion was made by examining the rates of B-cells and T-cells of the peripheral blood and the changes in rates of CD4+ T-cells and CD8+ T -cells of the blood sampled from the spleen and peripheral region. Especially the count of CD3+ CD4+ T-cells of the peripheral blood and the count of CD3+ CD4+ T-cells of the spleen the count of CD4+/ CD8+ T-cell of the peripheral blood and the spleen proved the significant effect of increasing immune responses statistically. Results :(1) The following are the summary of the results. (2) The percentage of B lymphocyte of peripheral blood was increased significantly in GJE group as compared with control group. (3) The percentage of CD3+ CD4+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (4) The percentage of CD3+ CD8+ T-cell of peripheral blood was not different statistically. (5) The percentage of CD4+/ CD8+ T-cell of peripheral blood was increased significantly in GJE group as compared with control group. (6) The percentage of CD3+ CD4+ T-cell of spleen was increased significantly in GJE group as compared with control group. (7) The percentage of CD3+ CD8+ T-cell was not different statistically. (8) The percentage of CD4+ /CD8+ T-cell was not different statistically. Conclusions : Gojineumja has an effect of increasing immune responses on white rats with deteriorated immunity caused by MTX.

• 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.

• Toxicological Research
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• v.17 no.2
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• pp.115-121
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• 2001

Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg$\cdot$ body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg$\cdot$b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg$\cdot$b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3$^{+}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) and CD3$^{-}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.

• Journal of Haehwa Medicine
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• v.17 no.1
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• pp.67-74
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• 2008

Objective: The purpose of this research is to examine the effects of Mahaenggamseok-tang-gagambang (MGTG) on CD3+ T cells, CD4+ T cells and CD8+ T cells in ovalbumin (OVA)-induced asthmatic mice. Methods: C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four a week) for asthma induction. Two experimental groups were treated with different concentrations of MGTG (400 mg/kg and 200 mg/kg) extract and cyclosporin A (10 mg/kg) for the later 8 weeks. At the end of the experiment, the mice lung was removed and analyzed CD3+ T cells, CD4+ T cells and CD8+ T cells by flow cytometer. Results: Numbers of CD3+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD4+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Numbers of CD8+ T cells in lung of the MGTG groups (200, 400 mg/kg) were significantly decreased compared with that of control group. Conclusion: The results of this study suggest that MGTG alleviated asthmatic hyperreactiviry through CD4+ and CD8+ T cells. Further study of relative cytokines is expected.