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Systemic and Mucosal Infection Program Protective Memory CD8 T Cells in the Vaginal Mucosa¹

Department of Microbiology, University of Tennessee, Knoxville, TN 37996

Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2–3x more Ag-specific CD8 T cells that coexpress both IFN- and TNF- in comparison to the intranasal route of infection. Expression of the integrin/activation marker CD103 (Eβ7) is low on vaginal mucosal Ag-specific CD8 T cells in comparison to gut mucosal intraepithelial lymphocytes. At memory, no differences are evident in the number, cytokine production, or protective function of Ag-specific CD8 T cells in the vaginal mucosa comparing the two routes of infection. However, differences persist in the cytokine profile of genital tract vs peripheral Ag-specific CD8 T cells. So although the initial route of infection, as well as tissue microenvironment, appear to influence both the magnitude and quality of the effector CD8 T cell response, both systemic and mucosal infection are equally effective in the differentiation of protective memory CD8 T cell responses against vaginal pathogenic challenge.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI05771901 and University of Tennessee start-up funds to T.M.O.

² Address correspondence and reprint requests to Dr. Thandi M. Onami, Department of Microbiology, University of Tennessee, Knoxville, TN 37996. E-mail address: tonami{at}utk.edu

³ Abbreviations used in this paper: i.n., intranasal; ILN, iliac lymph node; LCMV, lymphocytic choriomeningitis virus; IEL, intraepithelial lymphocytes; o-NALT, organized nasal-associated lymphoid tissue.