CD2 activation of human lamina propria lymphocytes reduces CD3 responsiveness

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.