scholarly journals Acquisition of an additional antigen specificity after mouse CD4 gene transfer into a T helper hybridoma.

1988 ◽  
Vol 167 (4) ◽  
pp. 1493-1498 ◽  
Author(s):  
W G Ballhausen ◽  
A B Reske-Kunz ◽  
B Tourvieille ◽  
P S Ohashi ◽  
J R Parnes ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
Recipient Cell ◽  
Surface Expression ◽  
T Cell Repertoire ◽  
T Helper ◽  
Antigen Specificity ◽  
Cell Repertoire ◽  
Increased Sensitivity ◽  
Additional Antigen

We have transfected the mouse CD4 gene into a beef insulin (BI)-specific murine T helper hybridoma that lacks CD4 surface expression. The CD4-expressing transfectants have acquired an additional reactivity for pork insulin (PI), which was not detectable in the original recipient cell. The transfectants' response to PI can be completely abrogated by anti-CD4 antibodies. The transfected clone showed a 50-fold increased sensitivity towards BI in comparison to the same CD4- hybridoma. These experiments suggest that CD4 may be important in determining the antigen fine specificity and, therefore, may also play a role in altering the T cell repertoire.

Mls AND THE HELPER T-CELL REPERTOIRE I. Mls as a regulator of T-helper cell activation

1988 ◽  
Vol 15 (1-3) ◽  
pp. 169-174 ◽  
Author(s):  
U. Hämmerling ◽  
M. Toulon ◽  
R. G. E. Palfree ◽  
M. K. Hoffmann
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Cell Repertoire ◽  
T Helper ◽  
Helper T Cell ◽  
Cell Repertoire

Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate

2009 ◽  
Vol 16 (2) ◽  
pp. 218-227 ◽  
Author(s):  
M. Chiarini ◽  
A. Sottini ◽  
C. Ghidini ◽  
C. Zanotti ◽  
F. Serana ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Glatiramer Acetate ◽  
T Helper Cells ◽  
T Cell Repertoire ◽  
T Helper ◽  
Cell Repertoire ◽  
Helper Cells ◽  
Cell Diversity ◽  
Multiple Sclerosis Patients

The immunomodulating activity of glatiramer acetate on T-cells of multiple sclerosis patients has only been partially clarified. The objective of this work was to investigate whether glatiramer acetate modifies thymic release of newly produced T-cells and the peripheral composition of the T-cell repertoire. T-cell receptor excision circles, thymic naive (CD4+CD45RA+CCR7 +CD31+) T helper cells, and central (CD4+CD45RA -CCR7+) and effector (CD4+CD45RA-CCR7 -) memory T-cells were evaluated in 89 untreated patients, 84 patients treated for at least 1 year, and 31 patients beginning treatment at the time of inclusion in the study and then followed-up for 12 months; controls were 81 healthy donors. The T-cell repertoire was analysed in selected samples. The percentage of thymicnaive T helper cells was diminished in untreated patients, but rose to control values in treated subjects; a decrease in central memory T-cells was also observed in treated patients. Follow-up patients could be divided into two subgroups, one showing unmodified thymicnaive T helper cells and T-cell diversity, the other in which the increased release of new T-cells was accompanied by modifications of the T-cell repertoire. Glatiramer acetate modifies the peripheral T-cell pool by activating a thymopoietic pathway of T-cell release that leads to a different setting of T-cell diversity and, likely, to a dilution of autoreactive T-cells.

scholarly journals Gene therapy for severe combined immunodeficiencies and beyond

2019 ◽  
Vol 217 (2) ◽  
Author(s):  
Alain Fischer ◽  
Salima Hacein-Bey-Abina
Keyword(s):  
Gene Therapy ◽  
T Cell ◽  
Gene Transfer ◽  
Insertional Mutagenesis ◽  
Ex Vivo ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Immunodeficiency ◽  
Combined Immunodeficiencies ◽  
Severe Combined Immunodeficiencies

Ex vivo retrovirally mediated gene therapy has been shown within the last 20 yr to correct the T cell immunodeficiency caused by γc-deficiency (SCID X1) and adenosine deaminase (ADA) deficiency. The rationale was brought up by the observation of the revertant of SCIDX1 and ADA deficiency as a kind of natural gene therapy. Nevertheless, the first attempts of gene therapy for SCID X1 were associated with insertional mutagenesis causing leukemia, because the viral enhancer induced transactivation of oncogenes. Removal of this element and use of a promoter instead led to safer but still efficacious gene therapy. It was observed that a fully diversified T cell repertoire could be generated by a limited set (<1,000) of progenitor cells. Further advances in gene transfer technology, including the use of lentiviral vectors, has led to success in the treatment of Wiskott–Aldrich syndrome, while further applications are pending. Genome editing of the mutated gene may be envisaged as an alternative strategy to treat SCID diseases.

Targeting self-antigens through allogeneic TCR gene transfer

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 870-877 ◽  
Author(s):  
Moniek A. de Witte ◽  
Miriam Coccoris ◽  
Monika C. Wolkers ◽  
Marly D. van den Boom ◽  
Elly M. Mesman ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
T Cell Receptor ◽  
Adoptive Transfer ◽  
Receptor Gene ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Receptor Genes ◽  
Self Antigens

Abstract Adoptive transfer of T-cell receptor (TCR) genes has been proposed as an attractive approach for immunotherapy in cases where the endogenous T-cell repertoire is insufficient. While there are promising data demonstrating the capacity of TCR-modified T cells to react to foreign antigen encounter, the feasibility of targeting tumor-associated self-antigens has not been addressed. Here we demonstrate that T-cell receptor gene transfer allows the induction of defined self-antigen–specific T-cell responses, even when the endogenous T-cell repertoire is nonreactive. Furthermore, we show that adoptive transfer of T-cell receptor genes can be used to induce strong antigen-specific T-cell responsiveness in partially MHC-mismatched hosts without detectable graft versus host disease. These results demonstrate the feasibility of using a collection of “off the shelf” T-cell receptor genes to target defined tumor-associated self-antigens and thereby form a clear incentive to test this immunotherapeutic approach in a clinical setting.

scholarly journals T Cell Receptor Complementarity Determining Region 3 Length Analysis Reveals the Absence of a Characteristic Public T Cell Repertoire in Neonatal Tolerance

2000 ◽  
Vol 191 (4) ◽  
pp. 695-702 ◽  
Author(s):  
Emanual Maverakis ◽  
Jonathan T. Beech ◽  
Stephen S. Wilson ◽  
Anthony Quinn ◽  
Brian Pedersen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
T Cell Repertoire ◽  
T Helper ◽  
Cell Repertoire ◽  
Freund's Adjuvant ◽  
Complementarity Determining Region ◽  
Helper Type

All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106–116, mount a T cell response using a “public” Vβ8.2Jβ1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role of T cell deletion or anergy within the mechanisms of observed neonatal “tolerance,” we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vβ8.2Jβ1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL–complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106–116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.

scholarly journals Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination

2020 ◽  
Vol 130 (2) ◽  
pp. 998-1009 ◽  
Author(s):  
Maike Smits ◽  
Katharina Zoldan ◽  
Naveed Ishaque ◽  
Zuguang Gu ◽  
Katharina Jechow ◽  
...  
Keyword(s):  
T Cell ◽  
T Helper Cells ◽  
Cd4 T Cell ◽  
T Cell Repertoire ◽  
T Helper ◽  
Cell Repertoire ◽  
Virus Elimination ◽  
Helper Cells ◽  
Follicular T Helper Cells

Peripheral T-cell repertoire alterations are common and affect outcome in large cell neuroendocrine lung carcinoma

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S53-S54
Author(s):  
P Christopoulos ◽  
M Schneider ◽  
F Bozorgmehr ◽  
W Engel-Riedel ◽  
C Kropf-Sanchen ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Carcinoma ◽  
Large Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire
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