• IMMUNE NETWORK
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• 제7권4호
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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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• 제31권4호
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• pp.175-180
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• 2007

고려홍삼이 HIV-1 감염자에게서 바이러스의 활발한 증식으로 유발된 면역계의 과활성화를 장기간에 걸쳐 억제하는지 살펴보기 위해 면역 활성화 지표인 soluble CD8항원(sCD8)을 측정하였다. HIV-1 감염 대조군 49명, zidovudine (ZDV) 복용군 22명, KRG 복용군 48명, KRG와 ZDV 병용군(49명)을 대상으로 하였다. HIV-1 감염 대조군에서는 혈청 sCD8 농도가 31-48개월 동안 33% 증가하였으며(P < 0.05), sCD8/CD8+T 림프구 비도 $21{\pm}13$개월동안 54% 증가하였다(P < 0.001). ZDV 복용군에서는 혈청 sCD8농도가 초기 6개월 동안은 감소하였으나 그 이후로는 서서히 증가하였으며, sCD8/CD8+T 림프구 비도 증가하였다. KRG 복용군은 sCD8 농도가 31-48개월 동안 45% 감소하였으며(P < 0.01), sCD8/CD8+T 림프구 비도 $19\;{\pm}\;11$개월 동안 19% 감소하였다(P < 0.05). 병용군에서는 sCD8 농도가 31-48개월 동안 29%(P < 0.01) 감소하였다. 추적관찰 기간 동안 각 군간의 sCD8 농도 변화가 명확한 차이를 보였으며, KRG 복용군에서는 ZDV 복용군에서 관찰된 'rebound현상'(sCD8이 초기에 감소하다가 다시 증가하는 경향)이 없었다. 결론적으로 본 연구에서는 HIV-1 감염환자에서 KRG를 장기간 복용시켰을 경우 sCD8 농도가 지속적으로 감소하여, KRG가 면역계의 소모적인 과활성화 상태를 방지함을 알 수 있었다.

• IMMUNE NETWORK
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• 제10권5호
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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.

• 대한의생명과학회지
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• 제1권1호
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• pp.27-35
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• 1995

HIV감염자는 질병의 진전에 무관하게 감염 후의 경과 시기에 따라서 CD4 T림프세포등 각종 면역상태를 나타내는 표지가 변한다 따라서 HW감염자의 질병진전을 예보하기 위하여서는 정기적으로 CD4등 각종표지를 측정하여 감염자의 질병상태를 monitoring하게 된다. 그러나 이러한 수치를 감염자관리에 적용하기 위하여서는 우리나라 일반인의 정상치를 파악하여 이를 지표로 해야 하므로 국내정상인의 각종 면역치에 대한 조사가 요구된다. 현재의 기준으로는 500이하로 떨어질 때에는 예방차원에서 AZT를 복용하게 되며 200이하로 떨어지면 질병의 유무에 관계없이 환자로 관리하게 된다. 본 연구에서는 한국인 185명의 감염자와 140명의 비감염자에 대하여 정기적으로 CD4 및 CD8T 림프세포와 CD4/CD8비를 측정하였다. 시험은 Flow cytometer(Facstar)를 이용하여 각각의 CD 분자에 대한 모노크로날 항체를 이용하여 2중혈광색소 염색방법으로 측정 하였다. HIV감염자의 CD4-T림프세포 절대수 및 백분율은 각각 462 및 18.2%이었는 반면, CD8의 수치는 1,170 및 47.0%이었다. 또한 CD4/CDB비는 0.43이었다. 이와는 대조적으로 비감염자의 경우, 한국인의 CD4의 평균 세포수는 886, 백분율은 32.9%이었으며, CD8 세포수는 730, 백분율은 26.8 그리고 CD4/CD8비는 1.31이었다. 외국인과 한국인과의 면역지표 수치를 비교하였을 때에 CD4세포수와 백분율, CD8의 백분율에서는 현저한 차이가 없었으나 외국인 비감염자의 경우 CD4백분율이 43.6%, CD8 T림프세포의 절대수가 560으로 한국인과 약간의 차이가 있었다. 따라서 HIV 감염자관리를 위한 면역지표측정시험에서의 각종수치의 정확한 해석을 위하여서는 한국인 비감염자수치를 고려해야할 것으로 판단된다.

• IMMUNE NETWORK
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• 제16권2호
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• pp.126-133
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• 2016

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes^hiCXCR3⁺ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44^hiCXCR3⁺ CD8 T cells. Initially, the majority of these CXCR3⁺ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44^hi phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3⁺ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

• IMMUNE NETWORK
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• 제23권5호
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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.

• Animal cells and systems
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• 제3권3호
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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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• 제12권3호
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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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• 제49권1호
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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]

• 동의생리병리학회지
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• 제21권2호
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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.