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 Augmented induction of CD8+ cytotoxic T-cell response and antitumour resistance by T helper type 1-inducing peptide

Immunology ◽  
2006 ◽  
Vol 117 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Takeshi Kikuchi ◽  
Shuichiro Uehara ◽  
Haruyuki Ariga ◽  
Takeshi Tokunaga ◽  
Ai Kariyone ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Helper ◽  
Helper Type

Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 868-876 ◽  
Author(s):  
Yuji Miura ◽  
Christopher J. Thoburn ◽  
Emilie C. Bright ◽  
Matthias Sommer ◽  
Susan Lefell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Graft Versus Host Disease ◽  
Cell Response ◽  
Effector T Cells ◽  
T Cell Response ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Graft Versus Host

Abstract Administration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis reveals that the effector T cells are highly conserved and recognize a peptide from the invariant chain peptide presented by MHC class II. Although human autologous GVHD effector T cells share a similar phenotypic specificity, clonality of the response in humans has not been determined. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining region 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD developed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of β-chain variable region (BV)16+ T cells were shared. Clonal expansions within BV15+ and BV22+ T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the other with HLA-DRB1*1502. These findings indicate that the discrete antigen-driven expansion of T cells is involved in autologous GVHD.

scholarly journals The Cytomegalovirus-Specific CD4+ T-Cell Response Expands with Age and Markedly Alters the CD4+ T-Cell Repertoire

2007 ◽  
Vol 81 (14) ◽  
pp. 7759-7765 ◽  
Author(s):  
Batoul Pourgheysari ◽  
Naeem Khan ◽  
Donna Best ◽  
Rachel Bruton ◽  
Laxman Nayak ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Immune Response ◽  
T Cell Repertoire ◽  
Immune Senescence ◽  
Cell Repertoire

ABSTRACT Immune function in the elderly is associated with a number of phenotypic and functional abnormalities, and this phenomenon of immune senescence is associated with increased susceptibility to infection. The immune response to pathogens frequently declines with age, but the CD8+ T-cell response to cytomegalovirus (CMV) is unusual, as it demonstrates a significant expansion over time. Here we have documented the CD4+ T-cell immune response to CMV in healthy donors of different ages. The magnitude of the CMV-specific CD4+ T-cell immune response increases from a mean of 2.2% of the CD4+ T-cell pool in donors below 50 years of age to 4.7% in donors aged over 65 years. In addition, CMV-specific CD4+ T cells in elderly donors demonstrate decreased production of interleukin-2 and less dependence on costimulation. CMV seropositivity is associated with marked changes in the phenotype of the overall CD4+ T-cell repertoire in healthy aged donors, including an increase in CD57+ expression and a decrease in CD28 and CD27 expression, a phenotypic profile characteristic of immune senescence. This memory inflation of CMV-specific CD4+ T cells contributes to evidence that CMV infection may be damaging to immune function in elderly individuals.

scholarly journals Endogenous Myelin Basic Protein Inactivates the High Avidity T Cell Repertoire

1998 ◽  
Vol 187 (12) ◽  
pp. 2055-2063 ◽  
Author(s):  
Oleg S. Targoni ◽  
Paul V. Lehmann
Keyword(s):  
T Cell ◽  
Myelin Basic Protein ◽  
Cell Response ◽  
Basic Protein ◽  
T Cell Response ◽  
High Avidity ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
C3h Mice ◽  
Selection Of

To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or negative selection of the MBP-specific T cell repertoire, we studied the T cell response to MBP in MBP-deficient shiverer and MBP-expressing congenic C3H mice. Immunization with MBP induced a vigorous T cell response in shiverer mice directed against a single I-Ak– restricted immunodominant determinant, the core of which is peptide MBP:79-87 (DENPVVHFF). Injection of this peptide induced a high avidity T cell repertoire in shiverer mice that primarily consisted of clones capable of recognizing the native MBP protein in addition to the peptide itself. These data show that endogenous MBP is not required for the positive selection of an MBP-specific T cell repertoire. C3H mice, in contrast, were selectively unresponsive to the MBP protein and injection of MBP:79-87 peptide induced a low avidity repertoire that could be stimulated only by the peptide, not by the protein. Therefore, endogenous MBP induced profound inactivation of high avidity clones specific for the immunodominant determinant making that determinant appear cryptic.

scholarly journals Dynamical System Modeling to Simulate Donor T Cell Response to Whole Exome Sequencing-Derived Recipient Peptides Demonstrates Different Alloreactivity Potential In HLA-Matched and Mismatched Donor-Recipient Pairs

2015 ◽  
Author(s):  
Badar Abdul Razzaq ◽  
Allison Scalora ◽  
Vishal Koparde ◽  
Jeremy Meier ◽  
Musa Mahmood ◽  
...  
Keyword(s):  
Dynamical System ◽  
T Cell ◽  
Binding Affinity ◽  
Cell Response ◽  
T Cell Response ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Cell Clones ◽  
Whole Exome ◽  
Alloreactive T Cell

Immune reconstitution kinetics and subsequent clinical outcomes in HLA matched recipients of allogeneic stem cell transplantation (SCT) are variable and difficult to predict. Considering SCT as a dynamical system, may allow sequence differences across the exomes of the transplant donors and recipients to be used to simulate an alloreactive T cell response, which may allow better clinical outcome prediction. To accomplish this, whole exome sequencing was performed on 34 HLA matched SCT donor-recipient pairs (DRP), and the nucleotide sequence differences translated to peptides. The binding affinity of the peptides to the relevant HLA in each DRP was determined. The resulting array of peptide-HLA binding affinity values in each patient was considered as an operator modifying a hypothetical T cell repertoire vector, in which each T cell clone proliferates in accordance to the logistic equation of growth. Using an iterating system of matrices, each simulated T cell clone’s growth was calculated with the steady state population being proportional to the magnitude of the binding affinity of the driving HLA-peptide complex. Incorporating competition between T cell clones responding to different HLA-peptide complexes reproduces a number of features of clinically observed T cell clonal repertoire in the simulated repertoire. These include, sigmoidal growth kinetics of individual T cell clones and overall repertoire, Power Law clonal frequency distribution, increase in repertoire complexity over time with increasing clonal diversity and finally, alteration of clonal dominance when a different antigen array is encountered, such as in stem cell transplantation. The simulated, alloreactive T cell repertoire was markedly different in HLA matched DRP. The patterns were differentiated by rate of growth, and steady state magnitude of the simulated T cell repertoire and demonstrate a possible correlation with survival. In conclusion, exome wide sequence differences in DRP may allow simulation of donor alloreactive T cell response to recipient antigens and may provide a quantitative basis for refining donor selection and titration of immunosuppression following SCT.

scholarly journals Potential Antiinflammatory Role of Insulin via the Preferential Polarization of Effector T Cells toward a T Helper 2 Phenotype

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 346-353 ◽  
Author(s):  
Alexander Viardot ◽  
Shane T. Grey ◽  
Fabienne Mackay ◽  
Donald Chisholm
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Insulin Receptor ◽  
T Cell Differentiation ◽  
Receptor Expression ◽  
T Helper ◽  
Type Response ◽  
Helper Type

Hyperglycemia in critical illness is a common complication and a strong independent risk factor for morbidity and death. Intensive insulin therapy decreases this risk by up to 50%. It is unclear to what extent this benefit is due to reversal of glucotoxicity or to a direct effect of insulin, because antiinflammatory effects of insulin have already been described, but the underlying mechanisms are still poorly understood. The insulin receptor is expressed on resting neutrophils, monocytes, and B cells, but is not detectable on T cells. However, significant up-regulation of insulin receptor expression is observed on activated T cells, which suggests an important role during T cell activation. Exogenous insulin in vitro induced a shift in T cell differentiation toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to Th2 ratio by 36%. This result correlated with a corresponding change in cytokine secretion, with the interferon-γ to IL-4 ratio being decreased by 33%. These changes were associated with increased Th2-promoting ERK phosphorylation in the presence of insulin. Thus, we demonstrate for the first time that insulin treatment influences T cell differentiation promoting a shift toward a Th2-type response. This effect of insulin in changing T cell polarization may contribute to its antiinflammatory role not only in sepsis, but also in chronic inflammation associated with obesity and type 2 diabetes.

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