PMID- 37014858
OWN - NLM
STAT- MEDLINE
DCOM- 20230406
LR  - 20230416
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 120
IP  - 15
DP  - 2023 Apr 11
TI  - Accessory cells precondition naive T cells and regulatory T cells for 
      cytokine-mediated proliferation.
PG  - e2217562120
LID - 10.1073/pnas.2217562120 [doi]
LID - e2217562120
AB  - Naive T cells and regulatory T cells, when purified, do not proliferate to the 
      gamma(c)-cytokines IL-2, IL-7, or IL-15, despite their expression of cognate cytokine 
      receptors. Dendritic cells (DCs) enabled the T cell proliferation to these 
      cytokines, through cell-to-cell contact, but independent of T cell receptor 
      stimulation. This effect lasted after separation of T cells from DCs, enabling 
      enhanced proliferation of the T cells in DC-depleted hosts. We propose calling 
      this a "preconditioning effect". Interestingly, IL-2 alone was sufficient to 
      induce phosphorylation and nuclear translocation of STAT5 in T cells, but could 
      not activate MAPK and AKT pathways and failed to induce transcription of IL-2 
      target genes. "Preconditioning" was necessary to activate these two pathways and 
      induced weak Ca(2+) mobilization independent of calcium release-activated 
      channels. When preconditioning was combined with IL-2, full activation of 
      downstream mTOR, 4E-BP1 hyperphosphorylation, and prolonged S6 phosphorylation 
      occurred. Collectively, accessory cells provide T cell preconditioning, a unique 
      activation mechanism, controlling cytokine-mediated proliferation of T cells.
FAU - Sato, Noriko
AU  - Sato N
AUID- ORCID: 0000-0002-9372-1725
AD  - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892.
AD  - Laboratory of Cellular Therapeutics, Molecular Imaging Branch, Center for Cancer 
      Research, National Cancer Institute, NIH, Bethesda, MD 20892.
FAU - Bamford, Richard N
AU  - Bamford RN
AD  - Transponics, Essex Junction, VT 05452.
FAU - Bryant, Bonita R
AU  - Bryant BR
AD  - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892.
FAU - Tagaya, Yutaka
AU  - Tagaya Y
AUID- ORCID: 0000-0002-1342-9282
AD  - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892.
FAU - Waldmann, Thomas A
AU  - Waldmann TA
AUID- ORCID: 0000-0003-4500-6660
AD  - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20230404
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytokines)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - *Cytokines/metabolism
MH  - *Interleukin Receptor Common gamma Subunit
MH  - T-Lymphocytes, Regulatory/metabolism
MH  - Interleukin-2/pharmacology/metabolism
MH  - Dendritic Cells/metabolism
MH  - Cell Proliferation
PMC - PMC10104559
OTO - NOTNLM
OT  - dendritic cells
OT  - gamma chain cytokine
OT  - naive T cells
OT  - proliferation
OT  - regulatory T cells
COIS- The authors declare no competing interest.
EDAT- 2023/04/05 06:00
MHDA- 2023/04/06 06:41
PMCR- 2023/04/04
CRDT- 2023/04/04 13:33
PHST- 2023/04/06 06:41 [medline]
PHST- 2023/04/04 13:33 [entrez]
PHST- 2023/04/05 06:00 [pubmed]
PHST- 2023/04/04 00:00 [pmc-release]
AID - 202217562 [pii]
AID - 10.1073/pnas.2217562120 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2217562120. doi: 
      10.1073/pnas.2217562120. Epub 2023 Apr 4.