Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys

作者：Chan Ming Liang; Petravic Janka; Ortiz Alexandra M; Engram Jessica; Paiardini Mirko; Cromer Deborah; Silvestri Guido; Davenport Miles P^*

来源：Proceedings of the Royal Society B, 2010, 277(1701): 3773-3781.

DOI：10.1098/rspb.2010.0972

• lymphocyte preservation
• lymphocyte proliferation/depletion
• CD4-positive T-lymphocytes
• Ki-67 antigen/analysis
• human/simian immunodeficiency virus
• mathematical model

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, 'natural hosts' of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to 'fuel the fire' of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection.

• 出版日期2010-12-22