While much work has been published on the dynamics of T cells-changes in representation of CD4 and CD8 cells-during HIV disease progression and treatment (HAART), much less is known about the changes in the functional subsets of T cells. Indeed, virtually nothing is known about the changes in the mucosal T cells-those cells residing in the gut or other peripheral sites (but can traffic via the blood and are found at low frequencies there). We are investigating the interrelationship of the mucosal and central immune systems, using our unique 17-color flow cytometric technology to derive as much information as possible from each animal. We are evaluating the functional status of the dozens of unique T cell subsets in blood, lymphoid organs, and mucosal sites during SIV disease and subsequent therapeutic regimens. We are also comparing these parameters in animals that have undergone vaccine regimens, to understand whether or not the vaccines have altered the specific immune response to the virus and the impact of such changes on clinical outcome.

Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$544,942
Indirect Cost
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State
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Pilipow, Karolina; Roberto, Alessandra; Roederer, Mario et al. (2015) IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy. Cancer Res 75:5187-5193
Roederer, Mario; Keele, Brandon F; Schmidt, Stephen D et al. (2014) Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature 505:502-8
Lugli, Enrico; Gattinoni, Luca; Roberto, Alessandra et al. (2013) Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells. Nat Protoc 8:33-42
Lugli, Enrico; Dominguez, Maria H; Gattinoni, Luca et al. (2013) Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest 123:594-9
Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy et al. (2012) Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates. Vaccine 30:5991-8
Bolton, D L; Song, K; Wilson, R L et al. (2012) Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge. Mucosal Immunol 5:41-52
Foulds, Kathryn E; Donaldson, Mitzi; Roederer, Mario (2012) OMIP-005: Quality and phenotype of antigen-responsive rhesus macaque T cells. Cytometry A 81:360-1
Lugli, Enrico; Mueller, Yvonne M; Lewis, Mark G et al. (2011) IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques. Blood 118:2520-9
Patterson, L Jean; Daltabuit-Test, Mara; Xiao, Peng et al. (2011) Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge. Virology 411:87-102
Waldmann, Thomas A; Lugli, Enrico; Roederer, Mario et al. (2011) Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. Blood 117:4787-95

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