Review
T cell responses to Chlamydia trachomatis

https://doi.org/10.1016/S1369-5274(02)00291-6Get rights and content

Abstract

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease in the United States, as well as the leading cause of preventable blindness worldwide. Immunity to C. trachomatis requires a variety of cell types, each employing an array of effector functions. Recent work has demonstrated that both CD4+ and CD8+ T lymphocytes play a major role in protective immunity to C. trachomatis, predominantly through their secretion of interferon-γ. This review describes the generation of acquired immunity to C. trachomatis and focuses on how T cells contribute to both protection and immunopathology.

Introduction

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the epithelial cells of the genital tract and conjunctivae. It can cause diseases that range from salpingitis and conjunctivitis to pelvic inflammatory disease, the blinding disease trachoma and the systemic infection lymphogranuloma venereum [1]. Chlamydia species have a unique lifestyle that is characterized by two distinct developmental forms. The infectious, metabolically inert elementary body (EB) survives outside the host cell, whereas the intracellular, non-infectious reticulate body (RB) replicates within a specialized vacuole called an inclusion. Intracellular replication necessitates an intimate association between the bacterium and the host cell that likely involves altering host cell functions in order to establish and maintain an environment conducive to replication within the inclusion. In addition, given that the compact Chlamydia genome lacks many essential biosynthesis genes, the bacteria must scavenge most of their nutrients, including ATP, from the host cell [2].

The intracellular lifestyle of Chlamydia undoubtedly influences which elements of host immunity will be effective in reducing the burden of organisms in the host. Although this review focuses on acquired immunity to C. trachomatis and the mechanisms by which T cells control the growth of Chlamydia, multiple immune mechanisms, including innate responses, are probably employed to control the growth and spread of this organism during infection. Innate resistance to Chlamydia, in both human populations and in inbred strains of mice with differential susceptibility to infection, is an exciting area of current investigation 3., 4., 5., 6.. Recruitment of inflammatory cells, such as macrophages, to the site of infection and the subsequent release of pro-inflammatory cytokines appear to be crucial for innate resistance to Chlamydia.

Section snippets

Acquired immunity to C. trachomatis

One approach to identifying the elements of acquired immunity important in resistance to C. trachomatis is to observe how the immune system responds to natural infection. However, immunity after a natural infection is not completely effective, as previous exposure to C.trachomatis offers only limited protection against re-infection. Most of this protection is serovar-specific and can be attributed largely to antibody specific for the major outer-membrane protein (MOMP), the primary determinant

Chlamydia-specific CD4+ and CD8+ T cells exert protective effects through secretion of interferon-γ

There is significant data demonstrating that both CD4+ and CD8+ T cells are involved in controlling C. trachomatis infection. In human and animal models, both T cell subsets are detected at the site of C. trachomatis infection 8., 9., 10.. In addition, adoptive transfer of either immune splenocytes or C. trachomatis-specific CD4+ or CD8+ T cells into infected mice has been shown to contribute to protection 11., 12., 13., 14., 15., 16.. These transferred CD4+ and CD8+ T cells limit C. trachomatis

The elements of the immune system most effective at limiting C. trachomatis replication probably also promote immunopathology

As described above, it is likely that IFN-γ-mediated activities are able to inhibit the growth of Chlamydia in infected individuals. However, experiments in humans and animals have shown that these activities often result in incomplete clearance of C. trachomatis 21., 34•., 37.. The inflammatory response that results from localized IFN-γ production is almost certainly to blame for many of the serious sequelae of C. trachomatis infection, such as tissue scarring. IFN-γ production by T cells at

Recognition of Chlamydia antigens by T cells depends on type of cell infected and compartmentalization of antigen

Dendritic cells are very efficient APCs that act as sentinels by internalizing pathogens, processing the pathogen-derived proteins into peptide fragments, and then migrating to secondary lymphoid organs, where they present these antigenic peptides to CD4+ and CD8+ Tcells [39]. In fact, Shaw et al. [40••] recently showed that adoptive transfer of dendritic cells pulsed with non-viable Chlamydia into naı̈ve mice afforded significant protection against subsequent challenge with viable Chlamydia.

Conclusions: both CD4+ and CD8+ T cell responses are required for optimal immunity to C. trachomatis

In many of their functions, CD4+ and CD8+ T cells are interdependent and redundant. Therefore, it is difficult to dissect the relative contributions of one subset by eliminating the other. This is particularly true when one considers that undermining the activity of CD4+ T cells may disrupt the activity of several other cell types. Selective depletion of either CD4+ or CD8+ T cells in experimental mice reduces the capacity of the animals to resolve C. trachomatis infection 17•., 52.. Several

Acknowledgements

We would like to thank Robert Brunham (University of British Columbia) and the members of the Starnbach lab for critical review of this manuscript.

References and recommended reading

Papers of particular interest, published within the annual period of review,have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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