scholarly journals Self recognition in allogeneic radiation bone marrow chimeras. A radiation- resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells

1981 ◽  
Vol 153 (5) ◽  
pp. 1286-1301 ◽  
Author(s):  
A Singer ◽  
KS Hathcock ◽  
RJ Hodes
Keyword(s):  
Bone Marrow ◽  
T Helper Cells ◽  
Keyhole Limpet Hemocyanin ◽  
The Self ◽  
T Helper ◽  
Spleen Cells ◽  
Self Recognition ◽  
Radiation Resistant ◽  
Bone Marrow Chimeras

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants. Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.

scholarly journals Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype.

1982 ◽  
Vol 155 (1) ◽  
pp. 339-344 ◽  
Author(s):  
A Singer ◽  
K S Hathcock ◽  
R J Hodes
Keyword(s):  
Nude Mice ◽  
T Helper Cells ◽  
Keyhole Limpet Hemocyanin ◽  
The Self ◽  
T Helper ◽  
Th Cells ◽  
Self Recognition ◽  
Accessory Cells ◽  
Host Origin

To examine the possibility that the thymus determines the I region-restricted self-recognition repertoire expressed by T helper (TH) cells, thymic chimeras were constructed by transplanting allogeneic neonatal thymic lobes into congenitally athymic nude mice. Spleen TH cells from the thymic chimeras were themselves of nude host origin but only cooperated with B+ accessory cells of the thymic haplotype for primary in vitro responses to sheep erythrocytes and trinitrophenyl conjugate of keyhole limpet hemocyanin. Thus, these experiments demonstrate that the self-recognition repertoire expressed by TH cells is determined by the H-2 phenotype of the intrathymic environment in which the TH cells had differentiated.

scholarly journals INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO

1971 ◽  
Vol 133 (6) ◽  
pp. 1325-1333 ◽  
Author(s):  
Klaus-Ulrich Hartmann
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Close Contact ◽  
Precursor Cells ◽  
Spleen Cells ◽  
High Concentrations ◽  
Thymus Cells ◽  
Bone Marrow Chimeras

Spleen cells of bone marrow chimeras (B cells) and of irradiated mice injected with thymus cells and heterologous erythrocytes (educated T cells) were mixed and cultured together (17). The number of PFC developing in these cultures was dependent both on the concentration of the B cells and of the educated T cells. In excess of T cells the number of developing PFC is linearly dependent on the number of B cells. At high concentrations of T cells more PFC developed; the increase in the number of PFC was greatest between the 3rd and 4th day of culture. Increased numbers of educated T cells also assisted the development of PFC directed against the erythrocytes. It is concluded that the T cells not only play a role during the triggering of the precursor cells but also during the time of proliferation of the B cells; close contact between B and T cells seems to be needed to allow the positive activity of the T cells.

scholarly journals Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures.

1977 ◽  
Vol 145 (3) ◽  
pp. 693-708 ◽  
Author(s):  
J S McDougal ◽  
D S Gordon
Keyword(s):  
Cell Cultures ◽  
T Helper Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Accessory Cell ◽  
T Helper ◽  
Spleen Cells ◽  
Helper Cells ◽  
Cell Carrier

Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1973 ◽  
Vol 138 (5) ◽  
pp. 1121-1132 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Baruj Benacerraf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Genetic Control ◽  
T Helper Cells ◽  
Cell Function ◽  
T Helper ◽  
Spleen Cells ◽  
Culture Initiation

The cellular requirements for the development of primary IgG GAT-specific PFC responses in cultures of spleen cells from responder, C57Bl/6, mice stimulated with GAT and GAT-MBSA and in cultures of spleen cells from nonresponder, SJL and B10.S, mice stimulated with GAT-MBSA were investigated. Macrophages were required for development of responses to GAT and GAT-MBSA in cultures of spleen cells from responder mice and for responses to GAT-MBSA in cultures of spleen cells from nonresponder mice. Macrophages from nonresponder mice supported the development of responses to GAT by nonadherent responder spleen cells, indicating that the failure of nonresponder mice to respond to GAT is not due to a macrophage defect. Furthermore, responder macrophages supported the responses of nonadherent, nonresponder spleen cells to SRBC and GAT-MBSA, but not to GAT. This indicates that the capacity to respond to GAT is a function of the nonadherent population which is composed of thymus-derived (T) helper cells and precursors of antibody-producing cells. Treatment of spleen cells with anti-theta serum and complement before culture initiation abolished PFC responses to GAT and GAT-MBSA thus establishing the requirement for T cells in the development of PFC responses to these antigens. Since precursors of antibody-producing cells in nonresponder mice are capable of synthesizing antibody specific for GAT after stimulation with GAT-MBSA and since the response to GAT is thymus-dependent, it appears that nonresponder mice lack GAT-specific helper T cell function.

Type I Interferons promote maintenance and function of follicular T helper cells in vitro

2019 ◽  
Author(s):  
S Ehrlich ◽  
K Wild ◽  
M Smits ◽  
K Zoldan ◽  
M Hofmann ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Type I Interferons ◽  
Type I ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
And Function

scholarly journals Generation of IL-8 and IL-9 Producing CD4+T Cells Is Affected by Th17 Polarizing Conditions and AHR Ligands

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Michaela Gasch ◽  
Tina Goroll ◽  
Mario Bauer ◽  
Denise Hinz ◽  
Nicole Schütze ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Immune Cell ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cells ◽  
Aryl Hydrocarbon

The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells underin vitroconditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.

scholarly journals Immunogenicity risk assessment for biotherapeutics through in vitro detection of CD134 and CD137 on T helper cells

mAbs ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1898831
Author(s):  
Sivan Cohen ◽  
Srividya Myneni ◽  
Anna Batt ◽  
Joyce Guerrero ◽  
Jochen Brumm ◽  
...  
Keyword(s):  
Risk Assessment ◽  
T Helper Cells ◽  
T Helper ◽  
Helper Cells

KS01.3.A Tumoral MHC class II expression in gliomas drives T cell exhaustion

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii3-ii3
Author(s):  
Y Chih ◽  
K Sahm ◽  
A Sadik ◽  
T Bunse ◽  
N Trautwein ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Helper Cells ◽  
Glioma Cell Line ◽  
Human Glioma ◽  
T Helper ◽  
Transcriptomic Data ◽  
Helper Cells ◽  
Mhcii Expression

Abstract BACKGROUND Neoepitopes are presented on major histocompatibility class II (MHCII) molecules. In glioma, for instance, the recurrent driver mutation IDH1R132H was shown to bear an MHCII-restricted epitope in preclinical and clinical vaccine studies. The general relevance of MHCII expression in glioma for antitumor immunity, however, remains unknown. Here we evaluate stromal and tumoral MHCII expression, functionality, and its association with survival in gliomas. MATERIAL AND METHODS Immunostaining of human glioma tissues was used to identify tumoral, endothelial, and microglial MHCII expression and to enumerate T cell infiltrates. To gain insights into tumoral MHCII expression, bulk transcriptomic data from TCGA and single-cell transcriptomic data from publicly available datasets were analyzed. MHC ligandome analyses of an MHCII+ glioma cell line and human glioma tissues were used to determine the functionality of MHCII in vitro and ex vivo. Functional in vitro co-culture assays with an HLA-DR-matched tetanus toxoid (TT) epitope-overexpressing glioma cell line and in vitro-expanded TT-reactive T cells from healthy donors were used to examine direct target recognition by T helper cells. CRISPR-Cas9-mediated knockout of MHCII in preclinical hypermutant glioblastoma cell line GL261 was employed to further validate the consequences of tumoral MHCII expression and to probe potential clinical intervention with existing therapies. RESULTS MHCII is expressed in the majority of gliomas and associated with increased infiltration of T cells. In 10% of the analyzed glioma tissues and a subset of single cells, tumoral MHCII expression is detected. Clinical and transcriptomic data reveal that tumoral MHCII is associated with poor prognosis, cytokine responses, immune inhibition and T cell differentiation. Ligandome analyses evidence presentation of peptides by MHCII molecules on glioma cells. In in vitro assays, TT-reactive T helper cells specifically produce IFNg when co-cultured with MHCII+ glioma cells upon the presence of co-stimulation. In agreement with the clinical data, preclinical murine models demonstrate that tumoral MHCII expression leads to reduced survival. Co-culture assay shows that tumoral MHCII results in upregulation of PD-1 on T helper cells antigen-specifically. Concordantly, immune checkpoint blockade (ICB) therapy slows the disease progression of mice carrying MHCII+ tumors. CONCLUSION MHCII is expressed in gliomas by a subset of tumor cells. Although tumoral MHCII is functional, it is associated with poor survival in both clinical data and preclinical models. T cell exhaustion induced by tumoral MHCII expression can, in part, be overcome by ICB in vivo. Further experiments are required to decipher tumor cell intrinsic and microenvironmental consequences of tumoral MHCII expression.

scholarly journals Investigation of Cytotoxic T Lymphocyte Function during Allorejection in the Anterior Chamber of the Eye

2020 ◽  
Vol 21 (13) ◽  
pp. 4660
Author(s):  
Hsin-Fang Chang ◽  
Marie-Louise Wirkner ◽  
Elmar Krause ◽  
Jens Rettig
Keyword(s):  
Immune Responses ◽  
Anterior Chamber ◽  
T Helper Cells ◽  
Cytotoxic T Lymphocyte ◽  
Diabetes Research ◽  
Lymphocyte Function ◽  
T Helper ◽  
Helper Cells

Cytotoxic T lymphocytes (CTL) are an essential part of our immune system by killing infected and malignant cells. To fully understand this process, it is necessary to study CTL function in the physiological setting of a living organism to account for their interplay with other immune cells like CD4+ T helper cells and macrophages. The anterior chamber of the eye (ACE), originally developed for diabetes research, is ideally suited for non-invasive and longitudinal in vivo imaging. We take advantage of the ACE window to observe immune responses, particularly allorejection of islets of Langerhans cells by CTLs. We follow the onset of the rejection after vascularization on islets until the end of the rejection process for about a month by repetitive two-photon microscopy. We find that CTLs show reduced migration on allogeneic islets in vivo compared to in vitro data, indicating CTL activation. Interestingly, the temporal infiltration pattern of T cells during rejection is precisely regulated, showing enrichment of CD4+ T helper cells on the islets before arrival of CD8+ CTLs. The adaptation of the ACE to immune responses enables the examination of the mechanism and regulation of CTL-mediated killing in vivo and to further investigate the killing in gene-deficient mice that resemble severe human immune diseases.

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