The main long-term objective of this work is to define the role of ?? T lymphocytes in SIV/HIV infections and utilize this information in our AIDS immunotherapy trials. Our 1998 efforts in this area focused on analyzing the reactivities of ?? T cells against various nonpeptidic ligands. We have developed methods for in vivo sensitization of rhesus macaque (Macaca mulatta) Vgamma9/Vdelta2 T cells. Specifically, intravenous injections of nonpeptidic antigens (DPG) induced an activated state of simian Vgamma9/Vdelta2 T cells which decreased after two months. The activation was detectable with a wide variety of phosphoantigens, such as ribose-1-phosphate (Rib-1-P), xylose-1-phosphate (Xyl-1-P), dimethylallyl-pyrophosphate (DMAPP), monoethyl-pyrophosphate (MEP), diphosphoglyceric acid (DPG), and isopentenyl-pyrophosphate (IPP), or natural (TUBAg-1) phosphoantigens. In parallel experiments, the influence of Vgamma9/Vdelta2 T cells on HIV replication was studied in vitro. The HIV infection of PBMC cultures led to absolute increases in Vgamma9/Vdelta2 T-cell numbers accompanied by decreasing levels of p24. The presence of strong Vgamma9/Vdelta2 T-cell activation resulted in a potent inhibition of HIV replication. Experiments performed in trans-well chambers showed that the in hibitory effect was (at least partially) mediated by soluble factors. Subsequent studies demonstrated that phosphoantigen-activated Vgamma9/Vdelta2 T cells produce substantial amounts of beta-chemokines MIP-1-alpha, MIP-1-beta and RANTES. Time course studies revealed that the beta-chemokine release occurred approximately 4 hours after the in vitro exposure to phosphoantigens. FUTURE DIRECTIONS 1n 1999, we plan to study the effects of in vivo modulations of ?? T-cell activities on the progression of SIV infections. KEY WORDS nonpeptidic antigens, ?? T cells

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000167-41
Application #
6454348
Study Section
Project Start
2001-05-01
Project End
2002-04-30
Budget Start
Budget End
Support Year
41
Fiscal Year
2001
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Kang, HyunJun; Mesquitta, Walatta-Tseyon; Jung, Ho Sun et al. (2018) GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition. Stem Cell Reports 11:197-211
Rhoads, Timothy W; Burhans, Maggie S; Chen, Vincent B et al. (2018) Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. Cell Metab 27:677-688.e5
Ellis-Connell, Amy L; Balgeman, Alexis J; Zarbock, Katie R et al. (2018) ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment. J Virol 92:
Park, Mi Ae; Jung, Ho Sun; Slukvin, Igor (2018) Genetic Engineering of Human Pluripotent Stem Cells Using PiggyBac Transposon System. Curr Protoc Stem Cell Biol 47:e63
Ellis, Amy; Balgeman, Alexis; Rodgers, Mark et al. (2017) Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques. Infect Immun 85:
Rodrigues, Michelle A (2017) Female Spider Monkeys (Ateles geoffroyi) Cope with Anthropogenic Disturbance Through Fission-Fusion Dynamics. Int J Primatol 38:838-855
Buechler, Connor R; Bailey, Adam L; Lauck, Michael et al. (2017) Genome Sequence of a Novel Kunsagivirus (Picornaviridae: Kunsagivirus) from a Wild Baboon (Papio cynocephalus). Genome Announc 5:
Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C et al. (2017) Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys. Toxicol Pathol 45:127-133
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732
Kalin, Ned H (2017) Mechanisms underlying the early risk to develop anxiety and depression: A translational approach. Eur Neuropsychopharmacol 27:543-553

Showing the most recent 10 out of 528 publications