Session 7Oral Abstract Presentations Immune Responses to HIV Session Day and Time: Tuesday 10 am - 12:15 pm Presentation Time: 10:45 Room: Ballroom B
30 Expression of Lymphocyte Homing Receptors by SIV-specific CD8+ T-cells in the Female Reproductive Tract of Rhesus Macaques M. Cromwell*1, X. Alvarez2, J. Altman3, S. Westmoreland1, S. Klumpp1, A.Luster4, A. Lackner2, P. Johnson1 1New England Natl Primate Res Ctr, Southborough, MA; 2Tulane Natl Primate Res Ctr, Covington, LA; 3Emory Vaccine Ctr at Yerkes, Atlanta, GA; and 4Massachusetts Gen Hosp, Harvard Med Sch, Boston
Background: Development of a vaccine capable of inducing genital T-cell responses to HIV is critical to preventing sexual transmission in women. Little information is currently available regarding the signals required for homing of virus-specific lymphocytes to genital mucosal tissues. In this study, we analyzed homing receptor expression by SIV-specific CD8+ T-cells in blood and cervicovaginal mucosa of rhesus macaques and identified chemokine producing cells in vaginal tissues.
Methods: SIV-specific CD8+ T-cells from blood and genital tissues were analyzed for receptor expression by multi-parameter flow cytometry using SIV Gag181-189/Mamu-A*01 tetramers. Cells expressing chemokines and chemokine receptors in vaginal tissue were identified using immunohistochemistry (IHC) and confocal fluorescence microscopy.
Results: CD8+ T-cells in genital mucosa were found to be significantly enriched for SIV-specific cells relative to peripheral blood (Ave = 14-fold; n = 7, p < 0.02 Wilcoxon signed rank test). The chemokine receptors CXCR3 and CCR5 were expressed on markedly higher percentages of CD8+ T-cells and SIV-specific CD8+ T-cells in genital mucosa than in blood. Expression of integrins aEb7 (CD103) and a4b7 was similar on virus-specific cells and the total CD8+ population in both blood and genital mucosa. CXCR3 and its chemokine ligand CXCL9 (Mig) were both detected in lymphoid aggregates in vaginal lamina propria. Both CD3+ T-cells and CD68+ cells were found to produce CXCL9 in vaginal tissues. These findings were observed in macaques infected with pathogenic or attenuated vaccine SIV strains.
Conclusions: These results indicate that SIV-specific T-cells are enriched in the CD8+ T-cell population of the female genital mucosa compared to peripheral blood. Expression of inflammatory chemokines such as CXCL9 may provide signals directing the trafficking of T-cells to the female reproductive tract.
