Asymptomatic Simian Immunodeficiency Virus Infection Decreases Blood CD4⁺T Cells by Accumulating Recirculating Lymphocytes in the Lymphoid Tissues

Abstract

Declining blood CD4+ T-cell counts mark the progress of simian immunodeficiency virus (SIV) disease in macaques and model the consequences of untreated human immunodeficiency virus infection in humans. However, blood lymphocytes are only a fraction of the recirculating lymphocyte pool, and their numbers are affected by cell synthesis, cell depletion, and distribution among blood and lymphoid tissue compartments. Asymptomatic, SIV-infected macaques maintained constant and nearly normal numbers of recirculating lymphocytes despite the decline in CD4+ T-cell counts. Substantial depletion was detected only when blood CD4+T-cell counts fell below 300/μl. In asymptomatic animals, changes in CD4+ T-cell distribution were more important than lymphocyte depletion for controlling the blood cell levels.

Total numbers of lymphocyte subsets in different lymph node regions of uninfected and SIV‐infected macaques

“…Thus, the decreased of CD4 + T-cells in blood could in part be explained by a redistribution of CD4 + T-cells to lymphoid organs. This conclusion is in line with a previous study showing no differences in the pool of circulating CD4 + T-cells between uninfected and SIV-infected asymptomatic animals when the extravasation was inhibited by pertussis toxin [28]. Several hypotheses have been put forward to explain the presumed different lymphocyte distribution between blood and lymphoid organs after immunodeficiency virus infections.…”

“…Although several studies have found indirect evidence [1,2,6,16,28], this finding provides the first direct proof for a redistribution of lymphocytes between blood and LNs. Most interestingly, although the total of CD4 + T-cell counts in blood were decreased and the CD4/CD8 ratios were reduced in LNs of the infected animals, the absolute numbers of CD4 + T-cells were increased in all LN regions of asymptomatic monkeys (data not shown).…”

Acute Effects of Pathogenic Simian-Human Immunodeficiency Virus Challenge on Vaccine-Induced Cellular and Humoral Immune Responses to Gag in Rhesus Macaques

“…Two macaques in group MMM that experienced large initial CD4 ϩ T-cell losses subsequently showed increasing CD4 ϩ T-cell levels that reached an average of 490 cells/l of blood. This value is at the low end of the normal range for age-matched animals (10). Two macaques in group GMM experienced large, initial CD4 ϩ T-cell losses and remained at low levels, with CD4 ϩ T-cell numbers below 50 cells/l of blood by 8 weeks after challenge.…”

Lymphocyte Activation during Acute Simian/Human Immunodeficiency Virus SHIV89.6PDInfection in Macaques

“…The absolute number of CD4 ϩ T cells per microliter of blood was determined from the percentage of lymphocytes double positive for CD2 and CD4 and the total number of lymphocytes per microliter of blood as determined by CBC. Values for virus-naive macaque (n ϭ 5) blood samples were 38.8% CD4 ϩ , 21.2% CD8 ϩ , and 16.6% CD20 ϩ lymphocytes, compared to inguinal lymph node samples with 39.6% CD4 ϩ , 16.8% CD8 ϩ , and 30.8% CD20 ϩ lymphocytes (27 The mesenteric LN and cecum samples from the day 8 i.vag. infected macaque were positive for viral RNA, while the spleen, thymus, and other LN were negative.…”