Defective CD4+T Cell Signaling in Murine AIDS: Uncoupling of the T Cell Receptor Complex from PIP2Hydrolysis

CD4+T cells from mice with murine AIDS (MAIDS) have been shown to be unable to respond to TCR stimulation as measured by proliferation, IL-2 production, or IL-2R upregulation, although responsiveness was restored with PMA and ionomycin. In this report we have demonstrated that the inability of MAIDS CD4+T cells to respond to CD3 stimulation was not associated with reduced surface expression of CD3, CD4, or CD28 and could not be overcome by costimulation with anti-CD28 antibody. However, MAIDS CD4+T cells failed to activate the PIP2hydrolysis pathway efficiently, resulting in diminished IP3production and reduced Ca2+mobilization compared to normal controls. Additionally, TCR signaling in MAIDS resulted in a reduction in the level of tyrosine phosphorylation of some proteins including deficient tyrosine phosphorylation of PLC-γ1, compared to normal CD4+T cells. These studies suggest that stimulation through the TCR in CD4+T cells from MAIDS-infected mice is uncoupled from the phosphotidylinositol hydrolysis pathway due to deficient activation of PLC-γ1.