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Sensory adaptation in naive peripheral CD4 T cells.

Smith K, Seddon B, Purbhoo MA, Zamoyska R, Fisher AG, Merkenschlager M - J. Exp. Med. (2001)

Bottom Line: Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck).Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen.Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, London W12 0NN, UK.

ABSTRACT
T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

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Maintenance of CD5 expression levels on naive peripheral CD4 T cells requires MHC contact. 107 APC-depleted Rag1o/o AND TCR transgenic LN cells from Aβ+/+ (bold) or Aβ+/o (thin line) donors were transferred intravenously to Rag1o/o MHCo/o hosts and host LN cells were analyzed for CD4, TCR Vα11 (the AND α chain), and CD5 by flow cytometry at the indicated times (histogram overlays are gated on CD4+ cells).
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fig2: Maintenance of CD5 expression levels on naive peripheral CD4 T cells requires MHC contact. 107 APC-depleted Rag1o/o AND TCR transgenic LN cells from Aβ+/+ (bold) or Aβ+/o (thin line) donors were transferred intravenously to Rag1o/o MHCo/o hosts and host LN cells were analyzed for CD4, TCR Vα11 (the AND α chain), and CD5 by flow cytometry at the indicated times (histogram overlays are gated on CD4+ cells).

Mentions: These data suggest that CD5 expression by peripheral CD4 T cells requires active maintenance, but they do not distinguish between a requirement for MHC contact or other factors (such as lymphokines; references 45 and 46) encountered in vivo. To discriminate between these possibilities we generated CD4 T cells that had been selected on different doses of the same pMHC ligands and followed their CD5 levels after transfer into deficient hosts. CD5 levels on Rag1o/o AND TCR transgenic CD4 cells reflected MHC class II dosage and was higher in Aβ+/+ mice than in Aβ+/o mice (mean fluorescence intensity 119 for Aβ+/+ versus 96 for Aβ+/o; n = 8; see Fig. 2 ex vivo). To ask whether CD5 levels are stable in vivo in the absence of MHC class II we adoptively transferred Rag1o/o AND CD4 T cells from Aβ+/+ and Aβ+/o donors into Rag1o/o MHCo/o hosts. 3 d after transfer, AND TCR transgenic CD4 cells showed reduced CD5 expression, but CD5 levels on cells from Aβ+/+ and Aβ+/o donors were still distinguishable (Fig. 2, d 3). 5 d after transfer CD5 expression by both populations was four to fivefold lower than on the day of transfer (compare Fig. 2 ex vivo and d 5). CD5 downregulation was selective (levels of CD4 and the transgenic TCR were not reduced) and occurred in the absence of early apoptotic markers as there was no increase in reactive oxygen species or loss of mitochondrial membrane potential (reference 47; data not shown). These data demonstrate that (i) CD5 expression declines on transfer of Rag1o/o AND TCR transgenic CD4 cells into MHCo/o Rag1o/o hosts and that (ii) the differences in CD5 levels found between Rag1o/o AND TCR transgenic CD4 cells selected on one or two doses of Ab (i.e., in Aβ+/o and Aβ+/+ mice, respectively) disappear on transfer into MHCo/o Rag1o/o hosts. We conclude that CD5 expression levels in naive peripheral CD4 T cells reflect continued MHC contact.


Sensory adaptation in naive peripheral CD4 T cells.

Smith K, Seddon B, Purbhoo MA, Zamoyska R, Fisher AG, Merkenschlager M - J. Exp. Med. (2001)

Maintenance of CD5 expression levels on naive peripheral CD4 T cells requires MHC contact. 107 APC-depleted Rag1o/o AND TCR transgenic LN cells from Aβ+/+ (bold) or Aβ+/o (thin line) donors were transferred intravenously to Rag1o/o MHCo/o hosts and host LN cells were analyzed for CD4, TCR Vα11 (the AND α chain), and CD5 by flow cytometry at the indicated times (histogram overlays are gated on CD4+ cells).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195983&req=5

fig2: Maintenance of CD5 expression levels on naive peripheral CD4 T cells requires MHC contact. 107 APC-depleted Rag1o/o AND TCR transgenic LN cells from Aβ+/+ (bold) or Aβ+/o (thin line) donors were transferred intravenously to Rag1o/o MHCo/o hosts and host LN cells were analyzed for CD4, TCR Vα11 (the AND α chain), and CD5 by flow cytometry at the indicated times (histogram overlays are gated on CD4+ cells).
Mentions: These data suggest that CD5 expression by peripheral CD4 T cells requires active maintenance, but they do not distinguish between a requirement for MHC contact or other factors (such as lymphokines; references 45 and 46) encountered in vivo. To discriminate between these possibilities we generated CD4 T cells that had been selected on different doses of the same pMHC ligands and followed their CD5 levels after transfer into deficient hosts. CD5 levels on Rag1o/o AND TCR transgenic CD4 cells reflected MHC class II dosage and was higher in Aβ+/+ mice than in Aβ+/o mice (mean fluorescence intensity 119 for Aβ+/+ versus 96 for Aβ+/o; n = 8; see Fig. 2 ex vivo). To ask whether CD5 levels are stable in vivo in the absence of MHC class II we adoptively transferred Rag1o/o AND CD4 T cells from Aβ+/+ and Aβ+/o donors into Rag1o/o MHCo/o hosts. 3 d after transfer, AND TCR transgenic CD4 cells showed reduced CD5 expression, but CD5 levels on cells from Aβ+/+ and Aβ+/o donors were still distinguishable (Fig. 2, d 3). 5 d after transfer CD5 expression by both populations was four to fivefold lower than on the day of transfer (compare Fig. 2 ex vivo and d 5). CD5 downregulation was selective (levels of CD4 and the transgenic TCR were not reduced) and occurred in the absence of early apoptotic markers as there was no increase in reactive oxygen species or loss of mitochondrial membrane potential (reference 47; data not shown). These data demonstrate that (i) CD5 expression declines on transfer of Rag1o/o AND TCR transgenic CD4 cells into MHCo/o Rag1o/o hosts and that (ii) the differences in CD5 levels found between Rag1o/o AND TCR transgenic CD4 cells selected on one or two doses of Ab (i.e., in Aβ+/o and Aβ+/+ mice, respectively) disappear on transfer into MHCo/o Rag1o/o hosts. We conclude that CD5 expression levels in naive peripheral CD4 T cells reflect continued MHC contact.

Bottom Line: Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck).Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen.Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, London W12 0NN, UK.

ABSTRACT
T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

Show MeSH