scholarly journals H-2 antigens of the thymus determinelymphocyte specificity

1978 ◽  
Vol 148 (3) ◽  
pp. 766-775 ◽  
Author(s):  
PJ Fink ◽  
MJ Bevan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Effector Cells ◽  
Minor Histocompatibility Antigens ◽  
Lymph Node Cells ◽  
Two Populations ◽  
Better Than

After immunization, normal H-2 heterozygous mice (for example H-2(b) × H-2(d)) generate two populations of cytotoxic effector T cells, one specific for target cells expressing H-2(b)-plus-antigen and the other specific for H- 2(d)-plus-antigen. With a multideterminant antigen, these two populations have about the same activity. We show here that the H-2 type of resident cells in the thymus determines the H-2 preference of cytotoxic T lymphocytes. F(1)(B 10 × B 10.D2) (H-2(b) × H-2 (d)) mice were thymectomized, lethally irradiated, and reconstituted with T-cell-depleted syngeneic hematopoietic cells. Groups of such ATXBM mice were grafted subcutaneously with neonatal thymus lobes from parental mice, either B10 (H-2 (b)) or B10.D2 (H-2(d)). 2-3 mo later, the mice were immunized against the minor histocompatibility antigens on F(1)(BALB/c × BALB.B) cells and assayed for cytotoxic T-cell activity. H-2(b) × H-2(d) ATXBM mice with H-2(b) thymus grafts responded to antigen-plus-H-2(b) much better than to antigen-plus-H-2(d), and vice versa for the mice with H-2(d) thymus grafts. As judged by antiserum treatment, the effector cells were of F(1) origin. To explore the possibility that the "thymus preference" may have been due to suppression of T-cell activity, nonimmune spleen and lymph node cells from normal H-2(b) × H-2(d) mice and cells from H-2(b) × H-2(d) mice bearing a homozygous thymus were mixed 1:1 and immunized in adoptive transfer. The mixture responded to antigen-plus-H-2(b) and antigen-plus-H-2(d) equally well, demonstrating that the cells that showed a "thymus preference" could not suppress a response to antigen in association with the nonthymic H-2 type. We conclude from these and other experiments that H-2 antigens present on resident cells of the thymus determine the spectrum of specificity of T cells which mature in that thymus and eventually make up the peripheral T- cell pool.

scholarly journals Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

1979 ◽  
Vol 149 (4) ◽  
pp. 856-869 ◽  
Author(s):  
T J Braciale
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Type A ◽  
Cross Reactivity ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Induction

Purified type A influenza viral hemagglutinin stimulates an in vitro cell-mediated cytotoxic cell response that exhibits a high degree of specificity for the immunizing hemagglutinin. The response magnitude is proportional to the hemagglutinin dose used for stimulation. The lytic activity of the effector cells is H-2 restricted. Analysis of the specificity of the response indicated that these cytotoxic T cells readily distinguish target cells expressing serologically unrelated hemagglutinin from target cells bearing hemagglutinins serologically related to the stimulating hemagglutinin. Further analysis of the fine specificity of cytotoxic T-cell recognition with serologically cross-reactive type A influenza hemagglutinins revealed a hierarchy of cross-reactivity among these hemagglutinins that was the converse of the serologic hierarchy. These results are discussed in terms of possible differences and similarities in the specificity repertoire of cytotoxic T cells and antibodies. Possible implications of these findings from the standpoint of cytotoxic T-cell induction are also discussed.

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

Induction of specific cytotoxic T-cell activity against xenogeneic target cells in carp (Cyprinus carpio)

2001 ◽  
Vol 62 (4) ◽  
pp. 599-603 ◽  
Author(s):  
Kiyoe Yamamoto ◽  
Masafumi Mukamoto ◽  
Shinobu Watarai ◽  
Hiroshi Kodama ◽  
Chihaya Nakayasu ◽  
...  
Keyword(s):  
T Cell ◽  
Cyprinus Carpio ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Carp Cyprinus Carpio

scholarly journals Delayed Clearance of Ehrlichia chaffeensis Infection in CD4+ T-Cell Knockout Mice†

2004 ◽  
Vol 72 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Roman R. Ganta ◽  
Chuanmin Cheng ◽  
Melinda J. Wilkerson ◽  
Stephen K. Chapes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Cell Mediated Immunity ◽  
Ehrlichia Chaffeensis ◽  
Wild Type

ABSTRACT Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis infections in three mouse strains with differing functional levels of helper T cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks. Major histocompatibility complex class II (MHCII) knockout, B6.129-Abb tm1 mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4+ T-cell-deficient, B6.129S6-Cd4 tm1Knw mice cleared the infection, but the clearance took 2 weeks longer than it did for wild-type mice. C57BL/6J mice resolved infection more rapidly following a second experimental challenge, but B6.129S6-Cd4 tm1Knw mice did not. The B6.129S6-Cd4 tm1Knw mice also developed active E. chaffeensis-specific immunoglobulin G responses that were slightly lower in concentration and slower to develop than that observed in C57BL/6J mice. E. chaffeensis-specific cytotoxic T cells were not detected following a single bacterial challenge in any mouse strain, including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity developed in all three mouse strains, including the MHCII and CD4+ T-cell knockouts, when challenged with a second E. chaffeensis infection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4+ T cells is critical for conferring rapid clearance of E. chaffeensis.

scholarly journals H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus.

1975 ◽  
Vol 141 (2) ◽  
pp. 502-507 ◽  
Author(s):  
P C Doherty ◽  
R M Zinkernagel
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Gene Complex ◽  
51Cr Release ◽  
Infected Cells ◽  
Immune Spleen Cells

Maximal cell-mediated lysis of targets infected with lymphocytic choriomeningitis virus occurs only within a H-2 compatible system. Syngeneic immune spleen cells are at least 100 times as effective as are allogeneic lymphocytes. Reciprocal restriction of cytotoxic T-cell activity has been shown to operative between H-2k, H-2d, and H-2b. Experiments with cogenic mice have localized the effect to the H-2 gene complex. Furthermore, the observation that lymphocytes from H-2a mice cause high specific 51Cr release from either H-2d virus-infected cells, indicates that identity at either the K or the D end of the H-2 gene complex is sufficient for this lytic interaction.

scholarly journals In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

1978 ◽  
Vol 148 (6) ◽  
pp. 1579-1591 ◽  
Author(s):  
L L Baum ◽  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Spleen Cells

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.

scholarly journals Selective inhibition of human T cell cytotoxicity at levels of target recognition or initiation of lysis by monoclonal OKT3 and Leu-2a antibodies.

1982 ◽  
Vol 155 (5) ◽  
pp. 1579-1584 ◽  
Author(s):  
U Landegren ◽  
U Ramstedt ◽  
I Axberg ◽  
M Ullberg ◽  
M Jondal ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Selective Inhibition ◽  
Lymphoid Cells ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Human T Cell ◽  
Killer Cell Activity

Out of a panel of seven monoclonal antibodies with affinity for human lymphoid cells, three were shown to prevent cytotoxic T cell activity, whereas none affected natural killer cell activity when applied without complement. Anti-OKT3 and anti-Leu-2a, with affinity for all T cells and the cytotoxic/suppressive subset, respectively were both shown to inhibit T killing by their interaction with the effector cell. For anti-OKT3, the inhibition remained after free antibody was washed away. Anti-Leu-2a, in contrast, induced a rapidly reversible inhibition. Using a single cell assay, anti-OKT3 was shown to reduce the lytic ability without affecting target cell binding, whereas anti-Leu-2a prevented the effectors from binding target cells.

scholarly journals LINC01355 Contributes to Malignant Phenotype of Oral Squamous Cell Carcinoma and Cytotoxic T Cell Infiltration via Activating Notch Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chen Zou ◽  
Siyuan Wu ◽  
Haigang Wei ◽  
Hailing Luo ◽  
Zhe Tang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Notch Signaling ◽  
Cd8 T Cells ◽  
Cell Activity ◽  
Cd8 T Cell ◽  
Cytotoxic T Cell ◽  
Migration And Invasion ◽  
Notch Signal

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC.

scholarly journals The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help.

1978 ◽  
Vol 147 (3) ◽  
pp. 897-911 ◽  
Author(s):  
R M Zinkernagel ◽  
G N Callahan ◽  
A Althage ◽  
S Cooper ◽  
J W Streilein ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Phenotypic Expression ◽  
Cell Activity ◽  
Thymic Epithelial Cells ◽  
Cytotoxic T Cell ◽  
Immunological Interactions

The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.

MDR-1 Recognition by Cytotoxic T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1346-1346
Author(s):  
Andreas G. Niethammer ◽  
Harald Wodrich ◽  
Markus Loeffler ◽  
Holger Lode ◽  
Robert Krempien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Carcinoma Cells ◽  
Cytotoxic T Cell ◽  
Target Antigen ◽  
Target Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Mdr 1

Abstract Acquired multidrug resistance (MDR) remains a major challenge in the treatment of cancer with chemotherapeutic drugs. It can be mediated by the upregulated expression of different proteins within the tumor cell membrane. Here we used murine MDR-1 as a target-antigen for the immunotherapy of cancer. We successfully demonstrated that peripheral T cell-tolerance can be broken by oral administration of a DNA vaccine encoding MDR-1 and carried by attenuated Salmonella typhimurium to secondary lymphoid organs. Thus, mice, immunized orally three times at 2-week intervals and challenged two weeks thereafter with either MDR-1 expressing CT-26 colon carcinoma cells or MDR-1 expressing Lewis lung carcinoma cells, revealed a significant increase in lifespan. This was evident, when compared to animals vaccinated with the empty control vaccine or to animals challenged with the maternal cell lines lacking overexpression of MDR-1. The immune response induced was antigen specific and CD8+ T cell-mediated. The presence of the target antigen led to upregulation of activation markers on CD8+ T cells and resulted in a strong cytotoxic T cell response as well as lysis of tumor target cells in vitro. We furthermore established the vaccine to be an effective treatment for established multidrug resistant tumor metastases resulting in a significantly increased lifespan of experimental animals. Absence of CD8+ T cells due to in vivo depletion led to abrogation of effectiveness. Taken together our results demonstrate, that T cell tolerance against the MDR-1 self antigen can be broken. It is anticipated that the combination of such an approach with chemotherapy could lead to more effective treatments of cancer.

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