Limits...
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.

Show MeSH
Polyclonal CD5low CD4 LN cells are hyperresponsive to CD3 ligation. Freshly isolated polyclonal LN cells were stained for CD4, CD5, and CD44 and separated into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations by cell sorting (A). LN cells were loaded with Fluo-4, and incubated with subsaturating concentrations of anti-CD3. Ca2+ responses were recorded immediately after cross-linking. Response traces by CD4+CD44low CD5low (black line) and CD4+CD44low CD5high (dashed line) cells are overlayed for comparison. Note the larger differential between resting and activated Ca2+ levels in CD5low cells (B) and the higher frequency of responding cells within the in CD5low population (C).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2195983&req=5

fig6: Polyclonal CD5low CD4 LN cells are hyperresponsive to CD3 ligation. Freshly isolated polyclonal LN cells were stained for CD4, CD5, and CD44 and separated into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations by cell sorting (A). LN cells were loaded with Fluo-4, and incubated with subsaturating concentrations of anti-CD3. Ca2+ responses were recorded immediately after cross-linking. Response traces by CD4+CD44low CD5low (black line) and CD4+CD44low CD5high (dashed line) cells are overlayed for comparison. Note the larger differential between resting and activated Ca2+ levels in CD5low cells (B) and the higher frequency of responding cells within the in CD5low population (C).

Mentions: To ask whether CD5 expression levels are predictive of CD4 T cell responsiveness also in vivo, we separated polyclonal LN cells isolated from wild-type mice into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations (Fig. 6 A) and compared their responsiveness to anti-CD3 followed by cross-linking (as in Fig. 5, top). The CD4+CD44lowCD5low population responded to CD3 ligation slightly but consistently better than CD4+CD44lowCD5high cells as reflected in a larger differential between resting and activated Ca2+ levels in CD5low cells (Fig. 6 B) and in a higher calculated frequency of responding cells (Fig. 6 C).


Sensory adaptation in naive peripheral CD4 T cells.

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

Polyclonal CD5low CD4 LN cells are hyperresponsive to CD3 ligation. Freshly isolated polyclonal LN cells were stained for CD4, CD5, and CD44 and separated into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations by cell sorting (A). LN cells were loaded with Fluo-4, and incubated with subsaturating concentrations of anti-CD3. Ca2+ responses were recorded immediately after cross-linking. Response traces by CD4+CD44low CD5low (black line) and CD4+CD44low CD5high (dashed line) cells are overlayed for comparison. Note the larger differential between resting and activated Ca2+ levels in CD5low cells (B) and the higher frequency of responding cells within the in CD5low population (C).
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Polyclonal CD5low CD4 LN cells are hyperresponsive to CD3 ligation. Freshly isolated polyclonal LN cells were stained for CD4, CD5, and CD44 and separated into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations by cell sorting (A). LN cells were loaded with Fluo-4, and incubated with subsaturating concentrations of anti-CD3. Ca2+ responses were recorded immediately after cross-linking. Response traces by CD4+CD44low CD5low (black line) and CD4+CD44low CD5high (dashed line) cells are overlayed for comparison. Note the larger differential between resting and activated Ca2+ levels in CD5low cells (B) and the higher frequency of responding cells within the in CD5low population (C).
Mentions: To ask whether CD5 expression levels are predictive of CD4 T cell responsiveness also in vivo, we separated polyclonal LN cells isolated from wild-type mice into CD4+CD44lowCD5low and CD4+CD44lowCD5high populations (Fig. 6 A) and compared their responsiveness to anti-CD3 followed by cross-linking (as in Fig. 5, top). The CD4+CD44lowCD5low population responded to CD3 ligation slightly but consistently better than CD4+CD44lowCD5high cells as reflected in a larger differential between resting and activated Ca2+ levels in CD5low cells (Fig. 6 B) and in a higher calculated frequency of responding cells (Fig. 6 C).

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