Phenotypic Changes in Growth-Arrested T Cell Hybrids: A Possible Avenue to Produce Functional T Cell Hybridoma

Kubota, Koichi; Iwabuchi, Kazuya

doi:10.3389/fimmu.2014.00229

Cited by 2 publications

(2 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Self-reactivity of hybridomas derived from Sf mice (Foxp3 GFP− and Foxp3 GFP+ ) was somewhat surprising since, in general, hybridomas do not inherit parental CD4 + cell effector features like Foxp3 expression or Th1/Th2 effector function. This is because intertypic hybrids of equal ploidy (mature CD4 + cell fused with thymoma) fail to express lineage specific traits of either parent 41 . Comparable proportions of hybridomas representing CD4 + Foxp3 − cells from Sf and adult DT-treated C57BL/6Foxp3 DTR/GFP mice were self-reactive, demonstrating that it is not a unique feature of TCR mini repertoire 22 .…”

Section: Discussionmentioning

confidence: 99%

Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice

et al. 2019

View full text Add to dashboard Cite

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3− T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3+ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4+Foxp3− cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including self-peptides that select them in the thymus. Our data thus suggest that identification of most potentially autoreactive CD4+ T cells in the peripheral repertoire is critical to harness or redirect these cells for therapeutic advantage.

show abstract

Section: Discussionmentioning

confidence: 99%

Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…T cell hybridomas are useful tools for studying antigen-specific cellular, molecular, and functional events at a monoclonal level [1–6]. Unlike primary T cell clones, which may eventually lose their antigen specificity over a period of time if left unstimulated, T cell hybridomas can maintain antigen specificity for extended periods of time because of their inherent ability to grow continuously in cultures [2, 5, 6].…”

Section: Introductionmentioning

confidence: 99%

Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas

Krishnan

Massilamany

Basavalingappa

et al. 2015

Journal of Immunological Methods

View full text Add to dashboard Cite

Antigen-specific, T cell hybridomas are useful to study the cellular, molecular and functional events, but their generation is a lengthy process. Thus, there is a need to develop robust methods to generate the hybridoma clones rapidly in a short period of time. To this end, we have demonstrated a novel approach using major histocompatibility complex (MHC) class II dextramers to generate T cell hybridomas for an autoantigen, proteolipid protein (PLP) 139-151. Using MHC class II dextramers assembled with PLP 139-151 as screening and sorting tools, we successfully obtained mono antigen-specific clones within seven to eight weeks. In conjunction with other T cell markers, dextramers permitted phenotypic characterization of hybridoma clones for their antigen specificity in a single step by flow cytometry. Importantly, we achieved successful fusions using dextramer+ cells sorted by flow cytometry as a starting population, resulting in direct identification of multiple antigen-specific clones. Characterization of selected clones led us to identify chemokine receptor, CCR4+ to be expressed consistently, but their cytokine-producing ability was variable. Our work provides a proof-of principle that the antigen-specific, CD4 T cell hybridoma clones can be generated directly using MHC class II dextramers. The availability of hybridoma clones that bind dextramers may serve as useful tools for various in vitro and in vivo applications.

show abstract

Phenotypic Changes in Growth-Arrested T Cell Hybrids: A Possible Avenue to Produce Functional T Cell Hybridoma

Cited by 2 publications

References 67 publications

Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice

Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice

Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas

Contact Info

Product

Resources

About