Different thresholds of T cell activation regulate FIV infection of CD4⁺CD25⁺ and CD4⁺CD25^aaa cells

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• 作者：Joshi ; Anjali ; Garg ; Himanshu ; Tompkins ; Mary B. ; Tompkins ; Wayne A.
• 关键词：Treg cells ; Latency ; Activation ; Reservoirs ; HIV ; FIV ; IL-2
• 刊名：Virology
• 出版年：2005
• 出版时间：May 10, 2005
• 年：2005
• 卷：335
• 期：2
• 页码：212-221
• 全文大小：490 K

文摘

Cellular activation plays an important role in retroviral replication. Previously, we have shown that CD4⁺CD25⁺ T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4⁺CD25⁺ and CD4⁺CD25⁻ cells under different stimulation conditions. Both CD4⁺CD25⁺ and CD4⁺CD25⁻ cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4⁺CD25⁺ cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4⁺CD25⁻ T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4⁺CD25⁻ cells to replicate FIV, it induces apoptosis in a high percentage of CD4⁺CD25⁺ T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4⁺CD25⁻ cells. These results suggest that CD4⁺CD25⁺ and CD4⁺CD25⁻ T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4⁺CD25⁺ and CD4⁺CD25⁻ cells to serve as potential reservoirs of a productive and latent FIV infection.