• 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.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.175-180
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• 2007

To evaluate whether there is a relation between Korean red ginseng (KRG)-intake and the suppression of immune hyperactivation in HIV-1-infected patients, we measured serum soluble CD8 (sCD8) over 31-48 months in 168 patients. They were divided into four groups; HIV-1-infected control (n = 49), zidovudine (ZDV) group (n = 22), KRG group (n = 48), and combination of KRG and ZDV group (n = 49). In control, sCD8 and the ratio of sCD8/CD8+ T cells significantly increased by 33% (paired t-test, P < 0.05) and 54% over $21\;{\pm}\;13$ months (P < 0.001), respectively. In ZDV group, sCD8 decreased within first 6 months and then showed steady increase and the ratio also increased over $19\;{\pm}\;10$ months. In KRG group, sCD8 and the ratio of sCD/CD8+ T cells continuously decreased by 45% (P < 0.01) and 19% over $19\;{\pm}\;11$ months (P < 0.05), respectively. In combination group, sCD8 gradually decreased by 29% (P < 0.01). There was a clear difference in the changes in serum sCD8 over time among 4 groups. There was no rebound phenomenon in KRG group as shown in ZDV group. These results suggest that KRG-intake suppresses immune hyperactivation state by HIV antigen itself in the HIV-infected patients.

• IMMUNE NETWORK
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• v.10 no.5
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• pp.153-163
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• 2010

Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

• 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.

• 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.

• 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.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1991.06a
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• pp.20-20
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• 1991

악성종양의 발생과 진행에 면역 방어기능이 중요한 역할을 하리라는 가설은 모두가 공감하는 사실이다. 이중 T-lymphocyte와 Natural killer cell (이하 NK cell이라함)은 종양 면역학에 특히 중요한 임파구로 이런 임파구의 혈액분포양상은 면역방어기능을 짐작할 수 있는 간접적인 자료가 될 수 있다. 저자들은 치료전 두경부 악성종양환자에서 혈액을 채취하여 T-lymphocyte와NK cell의 분포양상을 검사하고, 방사선치료 환자에서는 NK cell activity를 측정하였기에 다음과 같은 결과를 보고하는 바이다. 1) 두경부 악성 종양 환자군에서 CD3+ cell은 감소하고 NK cell은 증가하며 CD4/CD8 비율은 변화가 없었다. 2) 병변이 진행되면서 CD3+ cell과 CD4+ cell은 감소하고 NK cell은 증가하였으며 CD4/CD8 비율의 변화는 없었다. 3) 방사선치료에 의해 CD3+ cell과 CD4+ cell, CD4/CD8 비율은 감소하였고, NK cell과CD8+cell은 증가하였다. 4) 방사선치료에 의한 CD4/CD8 비율의 감소와, CD8+ cell의 증가는 NK cell의 증가에 의한 것이라 추정되고, NK cell을 제외하면 CB4/CD8 비율의 변화는 없었다. 5) 방사선치료 환자에서 NK cell activity는 증가하였고, 이런 증가가 T-lymphocyte기능의 감소를 보상해 주고 있었다.

• 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.