In vivo depletion of CD4(+)CD25(hi) regulatory T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus.
Regulatory T (Treg) cells are activated and suppress immune responses during infection, and are characterized as CD4(+)CD25(hi)FOXP3(+). Ex vivo studies demonstrate that Treg cells potentially suppress anti-HIV-1 T cell responses. Lentivirus-induced CD4(+)CD25(hi) Treg cells were first described in feline immunodeficiency virus (FIV)-infected cats. In the present study we demonstrate that anti-feline CD25 monoclonal antibody (mAb) therapy depletes Treg cells in FIV-infected cats for 4 weeks and does not exacerbate viral replication or proinflammatory cytokine production. Significant FIV-specific immune responses are revealed in Treg cell-depleted cats. These anti-FIV effector cells exist prior to Treg cell depletion and are not expanded while Treg cells are depleted. Importantly, cats receiving the Treg cell-depleting mAb are able to produce a robust humoral response to new antigen. We propose that short-term in vivo Treg cell depletion during chronic HIV-1 infection could provide a window of opportunity for therapeutic vaccination in individuals with controlled viral replication.
Mikkelsen
S Rochelle
SR
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. rmikkelsen@globalvaccines.org
Reckling
Stacie K
SK
Egan
Erin A
EA
Dean
Gregg A
GA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D015704:CD4 Antigens / Q000032:analysis; D002371:Cat Diseases / Q000276:immunology* / Q000821:virology; D002415:Cats; D005260:Female; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016180:Lentivirus Infections / Q000276:immunology / Q000662:veterinary*; D008212:Lymphocyte Depletion; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit
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