A<i>Chlamydia trachomatis</i>-Specific Th2 Clone Does Not Provide Protection against a Genital Infection and Displays Reduced Trafficking to the Infected Genital Mucosa

Hawkins, Raymond A.; Rank, Roger G.; Kelly, Kathleen A.

doi:10.1128/iai.70.9.5132-5139.2002

Cited by 58 publications

(39 citation statements)

References 45 publications

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“…Other investigators have attempted to increase the frequency of Chlamydia-specific T cells by transferring T cell clones of unknown specificity into Chlamydia-infected mice (17,26). However, because the transferred T cells are antigen-experienced and have been propagated through multiple rounds of restimulation, the response of these T cells cannot be used to model the initial encounter of naïve T cells with C. trachomatis.…”

Section: Because Murine Cd4mentioning

confidence: 99%

Monitoring the T cell response to genital tract infection

Roan

Gierahn

Higgins

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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To date, it has not been possible to study antigen-specific T cell responses during primary infection of the genital tract. The low frequency of pathogen-specific T cells in a naïve mouse makes it difficult to monitor the initial events after antigen encounter. We developed a system to examine the response of pathogen-specific T cells in the genital mucosa after intrauterine infection. We identified the protective CD4 ؉ T cell antigen Cta1 from Chlamydia trachomatis and generated T cell receptor (TCR) transgenic (tg) mice with specificity for this protein. By transferring TCR tg T cells into naïve animals, we determined that Chlamydia-specific T cells were activated and proliferated in the lymph nodes draining the genital tract after primary intrauterine infection. Activated T cells migrated into the genital mucosa and secreted IFN-␥. The development of Chlamydia-specific TCR tg mice provides an approach for dissecting how pathogen-specific T cells function in the genital tract.Chlamydia ͉ adaptive immunity ͉ T cell receptor transgenic M ost pathogens enter a mammalian host by penetrating mucosal surfaces such as the lung, intestine, or genitourinary tract. The prevalence of sexually transmitted diseases has prompted studies to understand how infection is established in the genital tract and how pathogens are cleared from this site. Despite the importance of T cells in controlling a number of genital pathogens, the behavior of pathogen-specific T cells in the genital mucosa is not well characterized. The major obstacle to studying primary T cell responses is the low frequency of antigen-specific T cells in naïve mice. Because it is difficult to identify and track endogenous pathogen-specific T cells before infection, T cell receptor (TCR) transgenic (tg) animals have been developed that express pathogen-specific TCRs. T cells from TCR tg animals can be labeled and transferred into recipient mice, boosting the number of naïve, pathogen-specific T cells so that they can be monitored during infection. Although TCR tg mice have been useful in the study of organisms that infect animals systemically or the tracking of the response of T cells to pathogens that infect the lung or intestine (1-5), they have not been used to examine infection of genital tissues.To develop a system for studying pathogen-specific T cell responses in the genital mucosa, we developed TCR tg mice specific for Chlamydia trachomatis. C. trachomatis is a major cause of sexually transmitted disease and the leading cause of preventable blindness worldwide. In the genital tract, chronic and often undiagnosed infection stimulates a marked inflammatory response that contributes to Chlamydia-associated sequelae such as ectopic pregnancy and infertility (6, 7). Both protective immunity against C. trachomatis and the pathologies associated with Chlamydia infection are mediated by T cells. In humans, T cells respond to C. trachomatis at the site of infection and appear to contribute to pathology (8). In mice, depletion of T cells results in loss of protec...

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Section: Because Murine Cd4mentioning

confidence: 99%

Monitoring the T cell response to genital tract infection

Roan

Gierahn

Higgins

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to its role in directly limiting Chlamydia replication, IFN-g also plays an important role in adaptive immunity as it can enhance the presentation of antigens to both CD4 + and CD8 + T cells (Gaczynska et al, 1993;Steimle et al, 1994). CD4 + T cell-derived IFN-g appears to protect against infection as an IFN-g-producing CD4 + T-cell clone, but not an IL-4-producing CD4 + T-cell clone, protected mice against Chlamydia genital infection (Hawkins et al, 2002).…”

Section: Effector Functions Of Cd4 + T Cellsmentioning

confidence: 99%

Immune-mediated control of Chlamydia infection

Roan

Starnbach²

2007

Cell Microbiol

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SummaryInfection with the bacterium Chlamydia trachomatis can lead to a variety of diseases, including ectopic pregnancy, infertility and blindness. Exposure of the host to C. trachomatis stimulates multiple innate and adaptive immune effectors that can contribute towards controlling bacterial replication. However, these effectors are often insufficient to resolve the infection and prevent re-infection, and the continued presence of C. trachomatis within the host may induce immune effectors to chronically produce inflammatory cytokines. This may eventually lead to the tissue pathologies associated with the infection. Reducing the incidence and sequelae of infection will ultimately require the development of a C. trachomatis vaccine that can stimulate sterilizing immunity while avoiding immune-mediated pathology.

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“…These include up-regulation of inducible nitric oxide synthase expression resulting in nitric oxide production by macrophages (7,26); induction of indoleamine 2,3-dioxygenase, which degrades intracellular stores of tryptophan, an amino acid that Chlamydia has only a limited ability to produce (26, 47); and downregulation of transferrin receptor expression on the surfaces of infected cells, which would decrease intracellular iron stores (26). Th1 cells secreting IFN-␥ have been shown to be protective in animal models (10,48), while Chlamydia-specific Th2 clones do not provide protection against genital infection (21). Antibody may also mediate protection by a number of mechanisms, including blocking the initial attachment of Chlamydia to epithelial cells and prevention of subsequent ascending infection, enhancing killing of opsonized Chlamydia by phagocytic cells, thereby limiting dissemination to distant sites and enhancing the resolution of intracellular infection by antibodydependent cellular cytotoxicity (42).…”

Section: Monitoring Clearance Of Intravaginal Inoculation By Real-timmentioning

confidence: 99%