Md. Marmor et al., Immobilization of glycosylphosphatidylinositol-anchored proteins inhibits T cell growth but not function, INT IMMUNOL, 11(9), 1999, pp. 1381-1393
Accumulating evidence suggests that proteins tethered to the plasma membran
e through glycosylphosphatidylinositol (GPI) anchors share common biologica
l properties. In the present study we demonstrate that GPI-anchored protein
s regulate T cell growth. Specifically anti-TCR-induced proliferation was p
rofoundly inhibited by co-immobilized mAb specific for Thy-1, CD48 and Ly6A
/E, However, neither IL-2 production nor the effector function of cytotoxic
T lymphocytes was impaired in these circumstances. Analysis of the IL-2 re
ceptor (IL-2R) signaling pathway revealed that the association of IL-2R bet
a and gamma chains with the Janus kinases, JAK1 and JAK3, was not perturbed
in the presence of mAb specific for GPI-linked proteins. However, in these
conditions, IL-2-mediated recruitment of IL-2R alpha, beta and gamma chain
s, resulting in the formation of the high-affinity hetero-trimeric IL-2R, w
as inhibited. The resulting phosphorylation of JAK1 and JAK3, indicative of
their activation states, was correspondingly reduced. These results charac
terize a novel state of T cell physiology in which effector function is mai
ntained, in the absence of clonal expansion. A physiological role for GPI-a
nchored proteins in the maintenance of cellular homeostasis and function is
discussed.