title: Early short-term antiretroviral therapy is associated with a reduced prevalence of CD8(+)FoxP3(+) T cells in simian immunodeficiency virus-infected controller rhesus macaques.
abstract: Regulatory T cells contain a mix of CD4 and CD8 T cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. Recent studies have shown that an increased prevalence of CD8(+)FoxP3(+) T regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (SIV)-infected rhesus macaques. Preventing an increase in the prevalence of CD8 T regulatory subsets is likely to lead to a better long-term outcome. Here we show that short-term antiretroviral therapy initiated within 1 week after SIV infection was associated with lower viral set point and immune activation after withdrawal of therapy as compared to untreated animals. Early short-term treated controller animals were found to have better SIV-specific immune responses and a significantly lower prevalence of immunosuppressive CD8(+)FoxP3(+) T cells. Lower levels of CD8(+)FoxP3(+) T cells coincided with preservation of CD4(+)FoxP3(+) T cells at homeostatic levels, and significantly correlated with lower immune activation, suggesting a role for viral infection-driven immune activation in the expansion of CD8(+)FoxP3(+) T cells. Interestingly, initiation of continuous therapy later in infection did not reduce the increased prevalence of CD8(+)FoxP3(+) T cells to homeostatic levels. Taken together, our results suggest that early antiretroviral therapy preserves the integrity of the immune system leading to a lower viral set point in controller animals, and prevents alterations in the homeostatic balance between CD4(+) and CD8(+) T regulatory cells that could aid in better long-term outcome.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Jeffy
authors.initials: J
authors.lastname: George
authors.forename: Egidio Brocca
authors.initials: EB
authors.lastname: Cofano
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lybarger
authors.forename: Mark
authors.initials: M
authors.lastname: Louder
authors.forename: Bernard A P
authors.initials: BA
authors.lastname: Lafont
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Mattapallil
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D016827:CD8 Antigens / Q000032:analysis; D051858:Forkhead Transcription Factors / Q000032:analysis; D007108:Immune Tolerance; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D016827:CD8 Antigens; D051858:Forkhead Transcription Factors