Stromal derived factor-1alpha induces apoptosis in activated primary CD4+ T cells

As well as its primary role in regulating the homing and retention of leukocytes in hematopoietic and lymphoid tissues, stromal-derived factor 1-alpha (SDF-1α), the high affinity ligand of CXCR4, can mediate an apoptotic stimulus in different cell types, including cells of hematopoietic origin. In particular, ligation of CXCR4 by SDF-1α or by HIV-1 gp120 can result in the induction of CD8+ T cell apoptosis We have investigated the effect of SDF-1α on the survival of primary CD4+ T cells. Although only a fraction (20-30%) of freshly isolated CD4+ T cells expressed detectable levels of surface CXCR4, virtually all (> 95%) cells showed a bright expression of surface CXCR4 after 24 h of culture. In this study we demonstrated that SDF-1α induces a slow and progressive increase of apoptosis in activated primary CD4+ T cells. The ability of SDF-1α to induce apoptosis in these cells was clearly related to the surface expression of CXCR4. However, primary resting CD4+ T cells were completely refractory to the apoptosis-inducing activity of SDF-1α, in spite of a high density of surface CXCR4. Surface CXCR4 thus cannot transduce an apoptotic signal unless CD4+ T cells are previously induced to proliferate. As HIV-1 disease is characterized by an initial phase of immune activation, the ability of SDF-1α to induce apoptosis in activated CD4+ T cells may represent an additional mechanism of CD4+ T cell depletion in HIV-1-infected patients