Despite intensive study, the immune responses associated with protective immunity against HIV infection remain poorly understood. Analysis of cell-mediated immune responses induced by live attenuated SIV offers an ideal research setting in which to define specific mechanisms that may play a role in mediating protection. Rhesus macaques vaccinated with SIV239?nef or SIV239?3 develop vigorous SIV-specific cytotoxic T lymphocyte response and CD8+ lymphocytes from animals infected with live-attenuated SIV strains are able to inhibit SIV replication through both MHC-restricted mechanisms and the production of soluble factors. Prospective analysis of SIV-specific CTL responses in animals infected with different live attenuated SIV strains suggests that induction of strong SIV-specific immune responses correlates with protection against vaginal challenge. The overall goal of this project is to extend our understanding of cell-mediated immune responses generated by live attenua ted SIV strains, both at systemic and mucosal sites, and to carry out experiments that more definitively address the role of cell-mediated immune responses in protective immunity. The cell-mediated immune responses induced by infection with attenuated SIV vaccines will be further characterized, including analysis of antigen-specific cytokine responses and characterization of soluble factors able to suppress SIV replication. Cytotoxic T lymphocyte responses will be correlated with protection against challenge with heterologous strains of SIV. The cell-mediated immune responses in mucosal sites will be analyzed prior to, and following, mucosal routes of immunization. Finally, adoptive transfer of T cells in genetically identical rhesus macaques will be utilized to determine the role of cell-mediated immune responses in mediating protective immunity. Information from these studies should provide valuable information about the role that cell-mediated immune responses play in mediated resistance against challenge with SIV and HIV. FUNDING NIH AI-43044 (Project 2, subcontract) PUBLICATIONS Zelinski-Wooten MB, Hutchison JS, Hess DL, Wolf DP, Stouffer, RL. A bolus of recombinant human follicle stimulating hormone at midcycle induces periovulatory events following multiple follicular development in macaques. Hum Reprod 13:554-560, 1998. Smith GD, Sadhu A, Wolf DP. Transient exposure of rhesus macaque oocytes to calyculin-A and okadaic acid stimulates germinal vesicle breakdown permitting subsequent development and fertilization. Biol Reprod 58:880-886, 1998. Liu DS, Connor WE, Wolf DP, Alexander M. Uneven distribution of desmosterol and docasahexaenoic acid in the heads and tails of rhesus monkey sperm. J Lipid Res 39:1404-1411, 1998. Mayerhofer A, Smith GD, Danilchik M, Levine J, Wolf DP, Dissen GA, Ojeda SR. Oocytes are a source of catecholamines in the primate ovary Evidence for a novel cell-cell regulatory loop. Proc Natl Acad Sci USA 95:10990-10995, 1998. Lawce M, Olson S, Wolf DP, Magenis R, Ellen R. Comparative mapping of human cosmid probes in rhesus monkey (Macaca mulatta) using fluorescence in situ hybridization. J Assoc Genetic Tech 24:37-43, 1998. Wolf DP, Meng L, Ely JJ, Stouffer RL. Recent progress in mammalian cloning. J Assist Reprod Genet 15:234-238, 1998. Smith GD, Sadhu A, Mathies S, Wolf DP. Characterization of protein phosphatases in mouse oocytes, Dev Biol 204:537-549, 1998. Mixon BA, Patton B, Wolf DP, Larson J. Pregnancy rates following intrauterine insemination (UI) with post-freeze processed vs. pre-freeze processed donor sperm. Fertil Steril (Suppl), p-605, 1998 (abstract #S-317). Larson JM, Mixon BA, Albin IA, Tep NL, Wolf DP, Johnson A. Internal semen analysis proficiency testing to ensure inter- and intra-technician statistical control. Fertil Steril (Suppl), p-607, 1998 (abstract #S-317). Sadler-Fredd K, Patton PE, Larson J, Eaton DL, Teramura D, Wolf DP. Adoption of a blastocyst culture program. Fertil Steril Program Supplement 0-266, 1998 (abstract 599).