• IMMUNE NETWORK
• /
• v.5 no.1
• /
• pp.23-29
• /
• 2005

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

• Parasites, Hosts and Diseases
• /
• v.40 no.3
• /
• pp.119-129
• /
• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.5
• /
• pp.484-488
• /
• 1994

Background : The antigen-specific receptor on the surface of most peripheral T lymphocytes is a disulfide-linked heterodimer composed of $\alpha$ and $\gamma$ subunits, noncovalently associated with CD3 polypeptides. Recently, a novel type of CD3-associated heterodimer was described on a T cell subset that does not express CD4 or CD8 molecules. This second type of TCR dimer is composed of chains encoded for by the $\gamma$- and $\delta$-TCR genes. These cells may exert both cytotoxic and lymphokine producing functions. Although it was reported that some ${\gamma}{\delta}$-TCR might recognize an MHC-linked determinant, the funεtion or physiologic ligand for this new receptor is not yet clear. It was found that ${\gamma}{\delta}$-TCR can react with 65 kD heat shock protein of M. tuberculosis, which suggests the possible protective role of ${\gamma}{\delta}$ T lymphocytes against tuberculosis. In our previous study, there was neither the increase in number nor the functional activation of ${\gamma}{\delta}$ T cells in the peripheral blood from patients with pulmonary tuberculosis. Now we report the distribution of ${\gamma}{\delta}$ T cells in the regional sites of M. tuberculosis infection, especial1y tuberculous lymphadenitis. Methods : Lymph nodes from patients with pathologically-proven tuberculous lymphadenopathy (n=5) and reactive hyperplasia (n=3) were used. Tissues were frozen in liquid nitrogen immediately after removal and stored below $-70^{\circ}C$. The cryostat sections of these frozen specimens were stained with anti-Leu-4 Ab, Identi-T TCR ${\delta}1$, and Identi-T ${\beta}F1$. The number of positively stained cells were counted at high power field. Results : The infiltration of ${\gamma}{\delta}$ T cells was significantly higher in the lymph nodes from patients with tuberculous lymphadenopathy than that with reactive hyperplasia ($16.3{\pm}10.3%$ vs. $1.7{\pm}1.5%$). Conclusion : These results suggest that ${\gamma}{\delta}$) T cells may play a role in the defense against M. tuberculosis infection, especially in the regional sites of infection.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.3
• /
• pp.239-247
• /
• 1994

Background: T cell mediated immunity is important in the defense mechanism of tuberculosis. Since ${\gamma}{\delta}$ T cell receptor was found to react with 65 kD heat shock protein of M.tuberculosis, there have been some reports on the role of ${\gamma}{\delta}$ T cells in the defense against M.tuberculosis. But until now, the role of the ${\gamma}{\delta}$ T cells in tuberculosis is not clear. Methods: We therefore measured the percentage of ${\gamma}{\delta}$ T cells of peripheral blood by flowcytometry before and after stimulation with Con-A, PPD and H37Ra lysate and compared between tuberculosis patients and healthy controls. Results: ${\gamma}{\delta}$ T cells of pheripheral blood in pulmonary tuberculosis patients was $7.5{\pm}5.2%$, showing no difference compared with healthy control($10.0{\pm}4.8%$). But IL-2R(+) ${\gamma}{\delta}$ T cells were higher in tuberculosis compared with healthy control($4.8{\pm}5.1%$ vs. $1.8{\pm}2.8%$). After stimulation with PPD or Con-A, the percentage of ${\gamma}{\delta}$ T cells showed no significant change, but IL-2R(+) ${\gamma}{\delta}$ T cells increased significantly in both tuberculosis($17.9{\pm}13.4%,\;57.6{\pm}20.2%$ respectively) and healthy control group($11.5{\pm}9.1%,\;80.8{\pm}9.3%$). After stimulation with H37Ra lysate, percentage of ${\gamma}{\delta}$ T cells showed increasing tendency in healthy control group, but it was not statistically significant. Conclusion: In this study, we could not demonstrate the role of ${\gamma}{\delta}$ T cells in the peripheral blood of pulmonary tuberculosis. It is suggested that further studies will be needed in the regional sites of M.tuberculosis infection.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.1
• /
• pp.44-51
• /
• 1997

Background : The changes of the composition in the T-lymphocyte are important as an immunological abnormality in the pathogenesis of tuberculosis. Previously, the second type of TCR dimer(${\gamma}{\delta}$ T lymphocyte) that did not express CD4 or CD8 molecules was found. In other reports the presence of this type of lymphocytes was increased in the initial stage of tuberculous infections. Method : To determine whether there are some differences in the T-lymphocyte subsets in the peripheral blood or pleural effusion between pleural tuberculosis and other pleurisy. Thirty patients with pleural effusion among the forty-nine patients were examined T-lymphocyte subset analysis(CD4+T-cell,CD8+ T-cell,${\gamma}{\delta}$ T-lymphocytes) with anti- Leu4, anti-Leu3a, anti-Lea2a, anti HLA-DR and anti-TCR-${\gamma}{\delta}$-1(Becton & Dickinson Co.). Results : The average age of the patients was 50 years old(17-81year). There were 33 males and 16 female patients. Patiensts with tuberculosis are 30cases(tuberculous pleurisy 15), lung cancer 12cases(malignant effusion 9) and pneumonia 7cases(parapneumonic effusion 6cases) In T lymphocyte subsets of pleural effusion, helper T lymphocyte(54.6 + 13.8 %) of tuberculous pleurisy was higher than that(36.2 + 25.3 %) of non-tuberculous pleurisy(p=0.04). The peripheral blood ${\gamma}{\delta}$ T-lymphocytes in tuberculousis was insignificantly higher than non-tuberculous patients(p= 0.24). The peripheral blood ${\gamma}{\delta}$ T-lymphocytes and pleural ${\gamma}{\delta}$ T-Iymphocytes in tuberculous pleurisy was insignificantly higher than in non-tuberculous pleurisy(p= 0.16, p= 0.12). Conclusion : The percentage of -${\gamma}{\delta}$ T lymphocytes among the total T-lymphocytes is not significantly increased in the peripheral blood or pleural effusion of the pleural tuberculosis. ${\gamma}{\delta}$ T lymphocytes is less useful as a diagnostic method of pleural tuberculosis.

• The Korea Journal of Herbology
• /
• v.21 no.1
• /
• pp.51-56
• /
• 2006

Objectives : To clarify the effects of Actinidia polygama and CsA on OVA-induced asthma model, we examined the influence of Actinidia polygama fructus extract (APF) and CsA on the number of regulatory T cells, NKT cells and ${\gamma}{\delta}$ T cells in murine model of asthma. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of OVA in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks and APF (400, 40 mg/kg) were orally administered 3 times a week for 8 weeks. Results : The suppressive effects of APF on asthma model were demonstrated by the increase the number of regulatory T cells, ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells. Conclusion : These results indicate that APF has a deep inhibitory effect on airway inflammation and hyperresponsiveness in murine model of asthma by increase the number of regulatory T cells, and ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells.

• IMMUNE NETWORK
• /
• v.15 no.3
• /
• pp.142-149
• /
• 2015

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.

• Fisheries and Aquatic Sciences
• /
• v.8 no.2
• /
• pp.56-64
• /
• 2005

Two distinct CD3 homologue genes, $CD3\gamma/\delta\;and\;CD\varepsilon$, were isolated from a olive flounder leukocyte cDNA library and a BAC library. $CD3\gamma/\delta$ consisted of 961 bp encoding 178 amino acid residues, and $CD3\varepsilon$ consisted of 1006 bp encoding 164 amino acid residues. When compared with other known CD3 peptide sequences, the most conserved region of the two olive flounder CD3 chain peptides are the cytoplasmic domain and the least conserved are the extracellular domain. A phylogenetic analysis based on the deduced amino acid sequence grouped the two olive flounder CD3 sequences with $CD3\varepsilon$ and $CD3\gamma/\delta$, respectively. The olive flounder CD3 cluster (consisting of $CD3\varepsilon\;and\;CD3\gamma/\delta$) spans only 10.4 kb. The $CD3\varepsilon\;and\;CD3\gamma/\delta$ genes are oppositely transcribed only 3.8 kb apart. Both olive flounder CD3 genes have five exons. The two olive flounder CD3 genes were predominantly expressed in PBLs, kidney, spleen, and gills.

• IMMUNE NETWORK
• /
• v.20 no.1
• /
• pp.5.1-5.15
• /
• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.406-411
• /
• 2011

Background: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant $V{\alpha}{\beta}$ TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. Methods: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells by using Gene Set Enrichment Analysis (GSEA) method. Results: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells. Conclusion: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.