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Updated: Aug 13, 2026
Isolation and Activation of Murine Lymphocytes
Published on: October 30, 2016
CD2 activation of human lamina propria lymphocytes reduces CD3 responsiveness
1Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. ebertec@vmdnj.edu
Insights
Lamina propria lymphocytes (LPLs) exhibit a constitutive activation state via the CD2 receptor, preferentially interacting with CD58 on monocytes. This CD2 activation diminishes their responsiveness to CD3 receptor stimulation, impacting T cell signaling.
Area of Science:
- Immunology
- Cellular Biology
- T cell activation
Background:
- Lamina propria lymphocytes (LPLs) are traditionally considered antigen-activated memory T cells.
- However, LPLs demonstrate a stronger response to CD2 receptor ligation than to CD3 receptor ligation by mitogenic antibodies.
- This suggests a unique activation profile distinct from typical T cell responses.
Purpose of the Study:
- To define the constitutive activation state of LPLs.
- To investigate the relationship between this constitutive activation and their hyporesponsiveness to CD3 receptor stimulation.
- To elucidate the specific interactions driving LPL activation and proliferation.
Main Methods:
- Assessed LPL activation by measuring the display of the T11(3) epitope, an activated CD2 marker.
- Investigated constitutive CD2 activation by blocking the CD2-CD58 interaction and monitoring spontaneous proliferation.
- Determined LPL recognition preferences by assessing proliferation and interferon-gamma (IFN-gamma) secretion upon interaction with CD58 or MHC molecules on monocytes.
- Evaluated CD3 hyporesponsiveness by stimulating LPLs with CD2 antibodies prior to CD3-induced proliferation assays.
Main Results:
- LPLs exhibit a heightened display of the T11(3) epitope, indicating a constitutively activated state.
- Blocking the CD2-CD58 interaction reduced spontaneous LPL proliferation, confirming constitutive CD2 activation.
- LPLs preferentially recognized CD58 on monocytes, leading to proliferation and IFN-gamma secretion, which was inhibited by blocking CD2-CD58 interaction.
- Prior CD2 stimulation significantly reduced subsequent CD3-induced proliferation, demonstrating CD3 hyporesponsiveness without inducing apoptosis or altering CD3 expression.
Conclusions:
- LPLs are constitutively activated through the CD2 receptor.
- LPLs preferentially interact with CD58 expressed on monocytes.
- CD2 receptor stimulation in LPLs leads to a state of hyporesponsiveness towards CD3 receptor-mediated activation.
Abstract:
Lamina propria lymphocytes (LPLs) are thought to be antigen-activated memory T cells. Yet, they respond better to ligation of the CD2 receptor than the CD3 receptor by mitogenic antibodies. This study defines their constitutive state of activation and relates it to their CD3 hyporesponsiveness. The activated state of LPLs was demonstrated by their heightened display of the activated CD2 epitope, T11(3). Constitutive CD2 activation was shown by the reduction in spontaneous proliferation when the CD2-CD58 interaction was blocked. LPLs preferentially recognized CD58 rather than the major histocompatibility complex molecules on monocytes, triggering proliferation and interferon-gamma (IFN-gamma) secretion that was inhibited by blocking the CD2-CD58 interaction. To determine whether CD2 activation of LPLs contributes to their CD3 hyporesponsiveness, they were first stimulated with mitogenic CD2 antibodies and then tested for CD3-induced proliferation. The responses were greatly reduced by prior CD2 stimulation compared with LPLs cultured in medium alone. This effect was not caused by apoptosis or by changes in CD3 expression induced by CD2 triggering. This study shows that LPLs are constitutively activated through CD2, that they preferentially recognize CD58 on monocytes and that CD2 stimulation leads to CD3 hyporesponsiveness.
