Both systemic and mucosal LCMV immunization generate robust viral-specific IgG in mucosal secretions, but elicit poor LCMV-specific IgA.

Immunoglobulins in secretions play a critical role in protection at mucosal surfaces. We examined the generation of viral-specific IgG and IgA in plasma and mucosal secretions of mice following systemic or mucosal immunization with lymphocytic choriomeningitis virus (LCMV), a widely used experimental model of viral infection. While there are early differences in humoral responses depending on the route of viral entry, we show that both routes generate comparably robust viral-specific IgG in plasma, vaginal, lung, and nasal secretions of immune mice. In contrast, LCMV elicited poor viral-specific IgA responses. Mice that were infected IN showed elevated viral-specific IgA in nasal and lung washes compared to IP-infected mice; however, LCMV-specific IgG overwhelmingly contributed to the humoral response in all mucosal secretions examined. Thus similarly to HIV-1, and several other mucosally-encountered microbial infections, these data suggest that LCMV infection fails to induce vigorous viral-specific IgA responses.

Systemic and mucosal infection program protective memory CD8 T cells in the vaginal mucosa.

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-gamma and TNF-alpha in comparison to the intranasal route of infection. Expression of the integrin/activation marker CD103 (alphaEbeta7) 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.