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. This project is aimed at delineating potential mechanistic differences of co-stimulatory pathways between CD4+ T cells from SIV disease susceptible rhesus macaques (RM) and SIV disease resistant sooty mangabeys (SM), based on the initial observation that adult sooty mangabey CD4+ T cells are resistant to in vitro anergy induction in contrast to rhesus macaques and human CD4+ T cells. Hence peripheral blood na?ve and memory CD4+ T cells are obtained and stimulated in vitro to comparatively evaluate pathways including IL-2 synthesis regulation, CREB/CREM and p300 complex assembly, mTOR and cyclin dependent kinase regulation. These studies have recently highlighted a main difference between SIV infected SM and RM in the observation that SM central memory antigen specific T cells fail to upregulate GRAIL, the gene related to anergy in lymphocytes, unlike RM or human central memory cells, therefore preserving the potential of these cells to become potent effectors in the SM monkey. In addition, an extension of previous studies that have identified dysfunction in polo-like kinases in CD4+ T cells from rhesus macaques following SIV infection, recent microarray kinase analyses delineated several differences in cell cycle intermediates between TCR activated CD4 T cells from SM and RM. The most salient ones were a marked increase in Cyclin D3, E2F3, Cdc45/MCM6, Cyclin B and RAD17 in RM CD4+ T cells which affect both the afferent G1-S and the efferent S-G2 cell cycle transition steps. These alterations are likely to promote increased T cell activation, turnover and apoptosis whereas these changes were not seen when comparing CD4 T cells from before and after SIV infection in SM. These studies are likely to open novel therapeutic alternatives based on selective blockade of specific kinases similar to experimental cancer immunotherapies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000165-49
Application #
7958185
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2009-05-01
Project End
2010-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
49
Fiscal Year
2009
Total Cost
$56,690
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Fonseca, Jairo A; McCaffery, Jessica N; Caceres, Juan et al. (2018) Inclusion of the murine IgG? signal peptide increases the cellular immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage vaccine. Vaccine 36:2799-2808
Tedesco, Dana; Thapa, Manoj; Chin, Chui Yoke et al. (2018) Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic ?? T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease. Gastroenterology 154:2178-2193
Robinson, Amy A; Abraham, Carmela R; Rosene, Douglas L (2018) Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience 40:31-47
Walker, Lary C (2018) Sabotage by the brain's supporting cells helps fuel neurodegeneration. Nature 557:499-500
Mascaro, Jennifer S; Rentscher, Kelly E; Hackett, Patrick D et al. (2018) Preliminary evidence that androgen signaling is correlated with men's everyday language. Am J Hum Biol 30:e23136
Forger, Nancy G; Ruszkowski, Elara; Jacobs, Andrew et al. (2018) Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques. Horm Behav 100:39-46
Claw, Katrina G; George, Renee D; MacCoss, Michael J et al. (2018) Quantitative evolutionary proteomics of seminal fluid from primates with different mating systems. BMC Genomics 19:488
Adekambi, Toidi; Ibegbu, Chris C; Cagle, Stephanie et al. (2018) High Frequencies of Caspase-3 Expressing Mycobacterium tuberculosis-Specific CD4+ T Cells Are Associated With Active Tuberculosis. Front Immunol 9:1481
Beck, Goichi; Maehara, Shunsuke; Chang, Phat Ly et al. (2018) A Selective Phosphodiesterase 10A Inhibitor Reduces L-Dopa-Induced Dyskinesias in Parkinsonian Monkeys. Mov Disord 33:805-814
Georgieva, Maria; Sia, Jonathan Kevin; Bizzell, Erica et al. (2018) Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses. Infect Immun 86:

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