Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251.
IL-2, the first cytokine discovered with T cell growth factor activity, is now known to have pleiotropic effects on T cells. For example, it can promote growth, survival, and differentiation of Ag-selected cells, or facilitate Ag-induced cell death of T cells when Ag persists, and in vivo, it is thought to contribute to the regulation of the size of adaptive T cell response. IL-2 is deficient in HIV-1 infection and has been used in the management of HIV-1-infected individuals undergoing antiretroviral therapy. In this study, we investigated how continuous low-dose IL-2 affected the CD4+ and CD8+ T cell response induced by two inoculations of a canarypox recombinant SIV-based vaccine candidate in healthy macaques chronically infected with SIVmac251. These macaques had normal levels of CD4+ T cells at the beginning of antiretroviral therapy treatment. Vaccination in the presence of IL-2 significantly augmented Gag-specific CD8+ T cell responses, but actually reduced Gag-specific CD4+ T cell responses. Although IL-2 at low doses did not change the overall concentration of circulating CD4+ or CD8+ T cells, it expanded the frequency of CD4+CD25+ T cells. Depletion of the CD4+CD25+ T cells in vitro, however, did not result in a reconstitution of Gag-specific CD4+ responses or augmentation of SIV-specific CD8+ T cell responses. Thus, we conclude that the decrease in virus-specific CD4+ T cell response may be due to IL-2-promoted redistribution of cells from the circulation, or due to Ag-induced cell death, rather than suppression by a T regulatory population.
Nacsa
Janos
J
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA.
Edghill-Smith
Yvette
Y
Tsai
Wen-Po
WP
Venzon
David
D
Tryniszewska
Elzbieta
E
Hryniewicz
Anna
A
Moniuszko
Marcin
M
Kinter
Audrey
A
Smith
Kendall A
KA
Franchini
Genoveffa
G
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018655:Lymphocyte Count; D008253:Macaca mulatta; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018449:SAIDS Vaccines