VIRUS-INDUCED CYTOKINES REGULATE CIRCULATING LYMPHOCYTE LEVELS DURINGPRIMARY SIV INFECTIONS

Decline in blood CD4(+) lymphocytes during primary symptomatic infecti ons with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4(+) cell loss from blood of macaques undergoing an acute primary SIV infection might be due to in creased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus, Th e findings indicate that rapid lymphocyte depletion following acute in fection is not selective for CD4(+) cells, correlates precisely with i ncreased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible, CD4/CD8 ratios in lymph nodes with high viral burdens r emain relatively unchanged despite lymphocyte loss from blood, Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration, These resul ts support a model of cytokine-induced lymphocyte extravasation to acc ount for the acute HIV/SIV-induced CD4(+) cell lymphopenia and raise q uestions regarding the extent to which altered lymphocyte migration pl ays a role in the gradual CD4(+) cell depletion throughout infection.