Role of NK cells in early host response to chlamydial genital infection

The cell-mediated immune response has been documented to be the major prote ctive immune mechanism in mice infected genitally with the agent of mouse p neumonitis (MoPn), a biovar of Chlamydia trachomatis. Moreover, there is st rong evidence to indicate that gamma interferon (IFN-gamma) is a major effe ctor mechanism of the cell-mediated immune response. Previous studies from this laboratory have also reported that the dominant cell population in the genital tract is the CD4 Th1 population When experiments were performed by the enzyme-linked immunospot assay, high numbers of cells producing IFN-ga mma were found in the genital tract, concomitant with resolution of the inf ection; however, in addition, an increase in IFN-gamma-producing cells whic h were CD4(-) was seen early in the infection. Since natural killer (NK) ce lls produce IFN-gamma and have been found to participate in the early respo nses in other infections, we hypothesized that NK cells are responsible for early IFN-gamma production in the murine chlamydial model. NK cells were q uantified by the standard YAC-1 cytotoxicity assay and mere found to appear in the genital tract as early as 12 h after intravaginal infection with Mo Pn. The cells were confirmed to be NK cells by abrogation of YAC-1 cell cyt otoxicity by treatment in vitro and in vivo with anti-asialo-GM1. The early IFN-gamma response could also be depleted by treatment,vith anti-asialo-GM 1, indicating that NIC cells were responsible for the production of this cy tokine. Of interest was our observation that depletion of NR cells also exa cerbated the course of infection in the mice and elicited a Th2 response, a s indicated by a marked increase in immunoglobulin G1 antibody. Thus, these data demonstrate that NK cells are not only responsible for the production of IFN-gamma early in the course of chlamydial genital tract infection but are also, via IFN-gamma, a significant factor in the development of the Th 1 CD4 response and in the control of the infection.