This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The adoptive transfer of antigen-specific CD8+ effector T cells (TE) is being used to treat human viral and malignant disease with some success. However, the inconsistent or short in vivo persistence of transferred TE has been identified as a limitation of this approach. T cell growth factors such as interleukin (IL)-2 have been used to support the survival of transferred T cells. However, high-dose IL-2 can cause systemic toxicity, induces the expansion of CD4+FoxP3+ regulatory T cells (Treg), which can inhibit antitumor immunity, and may promote activation?induced cell death of transferred TE. IL-15 is a novel cytokine that has a critical role in the maintenance of T-cell memory and may be an alternative to IL-2 for supporting transferred T-cell survival. We administered IL-15 (2.5?15 ?g/kg s.c.) to 8 macaques, either daily (n=3) or every 3 days (n= 5), and assessed toxicity and immunological effects. Daily IL-15 increased circulating NK and CD8+ T cells and expanded CD8+CD95+CCR7- effector memory (TEM) and CD95+CCR7+ central memory T cells (TCM). However, daily IL-15 (5?15 ?g/kg) accumulated in vivo, causing reversible toxicities. Intermittent IL-15 treatment was safe, increased NK cells and CD8+ TEM or TCM, without boosting the CD4+ Treg. We are currently evaluating the administration of IL-15 to support adoptively transferred CD8+ TE in macaques. As previously reported, TCM-derived CD8+ TE transferred without cytokines persisted in vivo at low levels of 0.2?0.8% of CD8+ cells. By contrast, TE given with IL-15 persisted for up to 2 years at high levels (up to 10 % of CD8+ lymphocytes) after treatment in 2 animals. The transferred TE reverted to the memory pool and migrated to memory niches. Thus, IL-15 may provide an alternative to IL-2 to support the persistence of transferred TE in human immunotherapy.
| Pham, Amelie; Carrasco, Marisa; Kiorpes, Lynne (2018) Endogenous attention improves perception in amblyopic macaques. J Vis 18:11 |
| Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4 |
| Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric (2018) Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion. Neural Comput 30:1209-1257 |
| Shushruth, S; Mazurek, Mark; Shadlen, Michael N (2018) Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP. J Neurosci 38:6350-6365 |
| Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2018) A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 115:E1108-E1116 |
| Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540 |
| Hasegawa, Yu; Curtis, Britni; Yutuc, Vernon et al. (2018) Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status. Sci Rep 8:15867 |
| Oleskiw, Timothy D; Nowack, Amy; Pasupathy, Anitha (2018) Joint coding of shape and blur in area V4. Nat Commun 9:466 |
| Balakrishnan, Ashwini; Goodpaster, Tracy; Randolph-Habecker, Julie et al. (2017) Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues. Clin Cancer Res 23:3061-3071 |
| Shooner, Christopher; Hallum, Luke E; Kumbhani, Romesh D et al. (2017) Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys. J Neurosci 37:8734-8741 |
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