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Alexandra Ortiz Laboratory of Guido Silvestri

Abstract #: THLBA102. Evidence for CD4+ T Cell-Mediated Immune Control of SIVmac 251 Infection in Rhesus Macaques Undergoing CD4+ Lymphocyte Depletion Prior to Infection. Alexandra Ortiz Laboratory of Guido Silvestri. Control of Post-Peak Viremia is Multi-Factorial. CD8+ T Cells

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Alexandra Ortiz Laboratory of Guido Silvestri

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  1. Abstract #: THLBA102 Evidence for CD4+ T Cell-Mediated Immune Control ofSIVmac251 Infection in Rhesus Macaques Undergoing CD4+ Lymphocyte Depletion Prior to Infection Alexandra Ortiz Laboratory of Guido Silvestri

  2. Control of Post-Peak Viremia is Multi-Factorial • CD8+ T Cells • Neutralizing Antibodies • CD4+ T Cells: • Immune effectors • Target cell availability Immune Effectors Target-cell availability

  3. Animals: • 5 depleted RMs 3 MamuA*01+ 2 MamuA*01- • 4 non-depleted RMs 2 MamuA*01+ 2 MamuA*01- • Antibody Treatment: • Cdf OKT4A HulgG1 Ab • Days: -57, -52, -48 and -45 • Infection: • 3000 ID50 SIVmac251i.v. • Sampling: • Blood (PBMCs) • Bone marrow (BM) • Lymph node (LN) • Rectal biopsy (RB) Immune Effectors Methods and Rationale Advantages: Quantitative restriction Homeostatic proliferation Preservation of transmission targets Functional primary CTLs Target-cell availability

  4. Antibody-Treatment Depleted CD4+ T Cells from Blood, BM and LNs but not RB BM LN Percent CD4+ T Cells RB Days p.i.

  5. CD4+ T Cell Depletion Resulted in Reduced Survival and Increased Viral Load

  6. Antibody-treated Animals Exhibit Altered CD4+ T Cell Dynamics Following SIV-Infection

  7. Depleted Animals Generate CD8+ T Cell and Antibody Responses During Acute SIV-Infection Control Day 4 p.i. Day 14 Day 21 Day 42 Chronic Depleted RUv6

  8. Conclusions • The availability of CD4+ T cells as target cells does not directly dictate post-peak viral decline. • CD4+ T cells are not necessary for the induction of primary CTL response. • CD4+ T cells are necessary for controlling post-peak viral load in an immune effector capacity.

  9. Acknowledgements Silvestri Lab Guido Silvestri Jill Adamski Steve Bosinger Paul Carnathan Barbara Cervasi Beth Cramer Jessica Engram Nick Francella Caitlin Goodman Katrina Nolan MirkoPaiardini Elane Reyes Jessica Taaffe Thomas Vanderford Laboratory of Microbiology, NIAID, NIH Jason Brenchley Nichole Klatt Yerkes National Primate Research Center Funding NIH-NIAID: R01-AI066998 Yerkes: RR00016 • University of Pennsylvania • Francisco González-Scarano • Sarah Ratcliffe • Elena Ryzhova • - Center for AIDS Research • - Flow Cytometry and Cell Sorting Core • Emory University • Cindy Derdeyn • Bing Li • Center for AIDS Research

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