10th Conference on Retroviruses and Opportunistic Infections Boston, MA USA - February 10 -14, 2003

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 30
M. Cromwell¹ , X. Alvarez², J. Altman³, S. Westmoreland¹, S. Klumpp¹, A.Luster⁴, A. Lackner², P. Johnson^1
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-A01 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.

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