Costimulation of T‐cell proliferation by anti‐l‐selectin antibody is associated with the reduction of a cdk inhibitor p27

Abstract

SummaryIn this study, we investigated the costimulatory activity of L-selectin in primary mouse T cells. Proliferation induced by immobilized anti-CD3 antibody was enhanced by immobilized anti-L-selectin antibody. In contrast to the anti-CD28 antibody, anti-L-selectin antibody did not enhance interleukin-2 (IL-2) expression. One of the cyclin-dependent kinase (cdk) inhibitors, p27, was reduced by costimulation with anti-L-selectin antibody, as with anti-CD28 antibody, suggesting that the enhancement of T-cell proliferation is the result of a reduced p27 level. Since anti-L-selectin antibody enhanced the activation of extracellular signal-regulated protein kinase (ERK) induced by anti-CD3 antibody, ERK plays an important role in signal integration during costimulation. These results suggest that the mechanism of T-cell costimulation is at least partially different between CD28 and L-selectin, although the two mechanisms share a common downstream event, a reduction of p27 level, as a critical biochemical event in the cell cycle progression of T cells.

Requirement of L-selectin for γδ T lymphocyte activation and migration during allergic pleurisy: Co-relation with eosinophil accumulation

“…Our in vitro studies confirmed that CD62L mediates OVA-induced γδ T lymphocyte proliferation, suggesting defective co-stimulatory signaling during antigen presentation. Supporting reports demonstrated that CD62L co-stimulation with specific antibody enhanced α-CD3 mAb-induced proliferation and expression of CD25 on T lymphocytes [24]. In addition, the inhibition of CD62L signaling blocked α-CD3 mAb-induced T cell proliferation, due to impaired activation, as determined by calcium influx and ZAP-70 phosphorylation [35].…”

“…On the right, representative dot plots show percentages of pleural CCL11 + γδ, IL-5 + γδ and IL-4 + γδ T lymphocytes. molecules are capable to associate with TCR/CD3 complex [24][25][26]. The fact that in vivo selectin blockade both impaired OVA-induced increased numbers of γδ T lymphocytes in thoracic lymph nodes and reduced the numbers of γδ T cells expressing the proliferating phenotype IL-2α receptor chain CD25 and c-fos transcriptional factor suggests diminished activation and primary proliferating responses [36][37][38].…”

“…Furthermore, CD62L also functions as a co-stimulatory signal in T lymphocytes and is involved in the proliferation of these cells [24]. Moreover, CD62L has also been shown to associate with TCR/CD3 complex, supporting the role of CD62L in T lymphocyte costimulatory signaling [25,26].…”

CD62L (L-Selectin) Down-Regulation Does Not Affect Memory T Cell Distribution but Failure to Shed Compromises Anti-Viral Immunity

“…These results, together with the observation that T cells isolated from inflammatory sites express low levels of CD62L (10 -12), have suggested that down-regulation of CD62L may be required to redirect activated T cells away from LN, however this hypothesis has not been tested directly. Although the primary function of CD62L is in LN homing, expression levels correlate directly with effector function of CD8 T cells (13) and signaling via CD62L has been shown to costimulate TCR proliferation (14). It is, therefore, possible that the level of CD62L expression may also regulate the proliferation, differentiation and/or survival of Ag-activated T cells.…”

YY1 binds to regulatory element of chicken lysozyme and ovalbumin promoters

“…The protein concentrations were determined using bicinchoninic acid (Sigma Chemical, MO, USA) with bovine serum albumin as a standard. An equal amount of protein was loaded on each lane of a 7.5% polyacrylamide gel and transferred to PVDF membrane followed by the detection with anti-YY1 antibody as reported previously (Nishijima et al 2005).…”