HIV gp120 alone may mediate lymphopenia and lymphadnopathy in HIV infected individuals (46.4)

Abstract

Abstract Lymphopenia is the hallmark of HIV infection and is thought to be mediated by virus infection and subsequent killing of CD4+ T cells. However, recent data suggests that decrease in peripheral CD4+ T cells may initially involve sequestration of these cells in secondary lymphoid tissues (SLT). T cell homing to SLT is facilitated by SLT-specific chemokines, CCL19 and CCL21 while egress from SLT requires expression of functional sphingosine-1-phosphate (S1P) receptors. As lymphadnopathy is observed in most HIV-1 infected individuals, we investigated the potential of HIV-1 envelope glycoprotein, gp120, to affect parameters of T cell homing to SLT. Normal human T cells were exposed to gp120 for 1 to 24h prior to migration induced by CCL19 or CCL21. We also investigated the effects of gp120 on responsiveness to S1P induced migration. We found that exposure to gp120 for 1h augmented, by 2-fold, chemoattraction induced by CCL19 and CCL21, but did not effect migration induced by the SLT independent chemokine CCL11. Conversely, these cells became completely unresponsive to S1P induced migration (2–3 fold migration blocked to 0). The gp120 mediated inhibition of migration was completely reversed by the p56lck inhibitor herbimycin A, indicating a requirement of CD4 signaling. Taken together our data indicates that gp120 alone could facilitate CD4+ T cell homing and sequestration in the SLT of HIV infected indiivduals.