Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections

Abstract

Decline in blood CD4+ lymphocytes during primary symptomatic infections 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 increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain 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 results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.

Distinct Cycling CD4+- and CD8+-T-Cell Profiles during the Asymptomatic Phase of Simian Immunodeficiency Virus SIVmac251 Infection in Rhesus Macaques

“…A loss of CD4 ϩ T cells in the blood compartment similar to that in tissues has also been reported by other groups during HIV or SIV infection (51,52,54,56). Sopper et al (61) also found that the total CD4…”

Characterization of Peripheral Blood Lymphocyte Subsets in Patients with AcutePlasmodium falciparumandP. vivaxMalaria Infections at Wonji Sugar Estate, Ethiopia

“…A remarkable loss of T cells with high expression of LFA-1 (CD11/CD18) during acute P. falciparum malaria has also been reported by others (4). These findings indicate the withdrawal of lymphocytes from the peripheral blood to body tissue or lymph nodes, where they are sequestered and remain trapped (22). In contrast, others have reported no significance difference in the WBC count, the percentages of CD4 ϩ and CD8 ϩ cells, or the CD4/CD8 ratio in P. falciparum patients (15).…”

Recurrence of Hepatitis-Associated Aplastic Anemia after a 10-year Interval

“…The present case showed lymphocytopenia, not only at the initial onset but also on recurrence. Lymphocytopenia and a decreased CD4/8 ratio could also be explained by the influence of IFN-gamma and/or TNF alpha, as previously described (15). In the animal model of autoimmune hepatitis, the intra-hepatic accumulation of CD8+ T cells was triggered and activated by Kupffer cells (16).…”