The importance of lymphocyte trafficking in regulating blood lymphocyte levels during HIV and SIV infections

In humans, blood is commonly monitored to provide surrogates of disease progression and assess immune status. However, the varied, rapid and atypical alterations in lymphocyte subsets which may occur in blood in response to pathogens, are not predictive of changes in the bulk Of the immune system. A hallmark of human and simian immunodeficiency virus (SIV) infections is the profound loss of blood CD4(+) lymphocytes, a feature widely accepted as being a consequence of direct or indirect viral killing of CD4(+) cells throughout the body. However; in recording declining CD4 counts and CD4/8 ratios in the blood, little attention has been paid to migratory behaviour or the composition and tissue distribution of various lymphocyte subsets. This article compares the lymphocyte subsets in blood and various tissues in normal and virus-infected individuals prior to and following drug treatment and indicates an absence of selective CD4+ cell decreases or increases, highlighting the importance of lymphocyte tracking and compartmentalization in regulating blood T cell levels and suggesting a re-evaluation of the currently favoured paradigm.