A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion.
- 1Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Abstract
A new human xeno-free T cell expansion strategy enabled T cell receptor α/β (TCRα/β)-driven autologous reactivity and continuous long-term IL-2-dependent expansion of an unconventional professional T cell antigen-presenting cell (T-APC) subset. Autologous T-APC cultures were obtained from small peripheral blood mononuclear cell samples that yielded over 1020-fold expansions by an approach that did not require cell purification or genetic manipulation. Primary T-APCs constitutively expressed major histocompatibility complex class II glycoproteins, costimulatory B7 molecules, and FOXP3 in long-term culture. Autologous expansion yielded both CD4+ and CD8+ T-APC subsets that expressed signature activation markers and rapid cell division over 1 to 2 mo of culture in the absence of exogenous mitogenic or antigenic stimuli. Autologous IL-2-driven expansion of CD4+ T-APCs required TCR engagement because continuous T cell proliferation was blocked by neutralizing monoclonal antibodies against CD4, and constitutive expression of CD40L was inhibited by neutralizing major histocompatibility complex class II monoclonal antibodies. Long-term expansion required continuous TGF-β exposure, which increased HLA-DR and CD25 expression with consequent enhancement of antigen presentation, autologous TCR recognition, and IL-2 responsiveness. Low IL-2/TGF-β concentrations favored CD25high CD69low PD1low T-APC subsets, whereas high IL-2/TGF-β concentrations favored CD25low CD69high PD1high T-APC subsets. T-APC presentation of agonistic self-antigens induced extensive blastogenesis of polyclonal syngeneic responder T cells, some of which differentiated de novo into exponentially expanding T-APC lines. Overall, this study reveals professional T-APC subsets that exhibit exponential autologous expansion in vitro via autologous self-presentation and agonistic TCR self-recognition. These T-APCs may regulate homeostatic self-reactivity of the human TCRα/β repertoire and may mediate, in part, autologous mixed lymphocyte reactions.
Related
- Promises of co-stimulatory inhibition for durable and repeatable AAV gene therapy
- YOLOv11-Pose-Based Tracking Reveals Neuropeptide F Regulation of Agonistic Behavior in Macrobrachium rosenbergii.
- Sex differences in agonistic social behavior: Effects of exercise and ovariectomy
- Lactobacilli-based postbiotic differentially affects chicken macrophage-like HD11 cells depending on stimulatory lipopolysaccharide dosage
- Deciphering the role of SNP variants of co-stimulatory genes in systemic lupus erythematosus: from genotype to protein expression
BibTeX
@article{smallwood2026human,
title = {{A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion.}},
author = {Christian K Smallwood and Sunny L Sneed and Chandler L Williford and Tylar S Roof and Mark D Mannie},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
year = {2026},
month = oct,
doi = {10.1093/jimmun/vkag274},
url = {https://europepmc.org/article/MED/42906129},
note = {CC BY},
}
RIS
TY - JOUR
TI - A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion.
AU - Christian K Smallwood
AU - Sunny L Sneed
AU - Chandler L Williford
AU - Tylar S Roof
AU - Mark D Mannie
PY - 2026
DA - 2026/10/01
JO - Journal of immunology (Baltimore, Md. : 1950)
DO - 10.1093/jimmun/vkag274
UR - https://europepmc.org/article/MED/42906129
AB - A new human xeno-free T cell expansion strategy enabled T cell receptor α/β (TCRα/β)-driven autologous reactivity and continuous long-term IL-2-dependent expansion of an unconventional professional T cell antigen-presenting cell (T-APC) subset. Autologous T-APC cultures were obtained from small peripheral blood mononuclear cell samples that yielded over 1020-fold expansions by an approach that did not require cell purification or genetic manipulation. Primary T-APCs constitutively expressed major histocompatibility complex class II glycoproteins, costimulatory B7 molecules, and FOXP3 in long-term culture. Autologous expansion yielded both CD4+ and CD8+ T-APC subsets that expressed signature activation markers and rapid cell division over 1 to 2 mo of culture in the absence of exogenous mitogenic or antigenic stimuli. Autologous IL-2-driven expansion of CD4+ T-APCs required TCR engagement because continuous T cell proliferation was blocked by neutralizing monoclonal antibodies against CD4, and constitutive expression of CD40L was inhibited by neutralizing major histocompatibility complex class II monoclonal antibodies. Long-term expansion required continuous TGF-β exposure, which increased HLA-DR and CD25 expression with consequent enhancement of antigen presentation, autologous TCR recognition, and IL-2 responsiveness. Low IL-2/TGF-β concentrations favored CD25high CD69low PD1low T-APC subsets, whereas high IL-2/TGF-β concentrations favored CD25low CD69high PD1high T-APC subsets. T-APC presentation of agonistic self-antigens induced extensive blastogenesis of polyclonal syngeneic responder T cells, some of which differentiated de novo into exponentially expanding T-APC lines. Overall, this study reveals professional T-APC subsets that exhibit exponential autologous expansion in vitro via autologous self-presentation and agonistic TCR self-recognition. These T-APCs may regulate homeostatic self-reactivity of the human TCRα/β repertoire and may mediate, in part, autologous mixed lymphocyte reactions.
SN - 0022-1767
SN - 1550-6606
ER -