Different thresholds of T cell activation regulate FIV infection of CD4+CD25+ and CD4+CD25- cells.
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.
Joshi
Anjali
A
Immunology Program, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Garg
Himanshu
H
Tompkins
Mary B
MB
Tompkins
Wayne A
WA
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002415:Cats; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2; D003208:Concanavalin A