T Lymphocyte Immunity in Host Defence against Chlamydia trachomatis and Its Implication for Vaccine Development

Abstract

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes several significant human infectious diseases, including trachoma, urethritis, cervicitis and salpingitis, and is an important cofactor for transmission of human immunodeficiency virus. Until very recently, over three decades of research effort aimed at developing a C trachomatis vaccine had failed, due mainly to the lack of a precise understanding of the mechanisms for protective immunity. Although most studies concerning protective immunity to C trachomatis have focused on humoral immune responses, recent studies have clearly shown that T helper-1 (Th1)-like CD4 T cell-mediated immune responses play the dominant role in protective immunity. These studies suggest a paradigm for chlamydial immunity and pathology based on the concept of heterogeneity (Th1/Th2) in CD4 T cell immune responses. This concept for chlamydial immunity offers a rational template on which to base renewed efforts for development of a chlamydial vaccine that targets the induction of cell-mediated Th1 immune responses.

Adoptive Transfer of CD8α+ Dendritic Cells (DC) Isolated from Mice Infected with Chlamydia muridarum Are More Potent in Inducing Protective Immunity Than CD8α− DC

“…Although the key mechanism underlying the protective responses to Chlamydia is yet to be addressed, significant advances have been made in recent years largely due to the progress in experimental studies using murine models and epidemiological studies in humans (9,10). Chlamydia muridarum, formally called C. trachomatis mouse pneumonitis (MoPn), 2 is commonly used in mouse models of respiratory and genital tract infections (10).…”

“…Chlamydia muridarum, formally called C. trachomatis mouse pneumonitis (MoPn), 2 is commonly used in mouse models of respiratory and genital tract infections (10). It has been demonstrated that the pattern of cytokine responses is important in the regulation of immune responses to Chlamydia (11,12), and T cell-mediated immunity is the major protective mechanism against chlamydial infection (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

“…It was reported that trachoma patients with severe conjunctival scarring show impaired cell-mediated immune responses and low IFN-␥ production with high levels of IgG Ab production (24 -26). We previously found that the mouse strain that produces higher organism-driven IFN-␥ production shows significantly more resistance to chlamydial infection (10,17) and that IFN-␥ gene knockout (KO) mice, IL-12 KO mice, and IL-18 KO mice exhibit much more serious diseases when compared with wild-type mice (27,28). Studies by other groups also demonstrated the extreme importance of IFN-␥ and Th1 immune responses in host defense against chlamydial infection (14,22,23,25).…”

NK T Cell Activation Promotes Chlamydia trachomatis Infection In Vivo

“…The difference in the cytokine patterns have been correlated with the severity of disease progression in both human subjects and animal models. In particular, Th1 responses have been found to be associated with protection, whereas Th2 responses are associated with immunopathology (22)(23)(24)(25)(26). Thus far, there is no report on the role of NKT in chlamydial infection and the effect of NKT on adaptive immune responses to chlamydial infection.…”

Mathematical modelling of Chlamydia

“…It has been suggested that cell-mediated immunity, not humoral immunity, plays the dominant role in protective immunity against Chlamydia [12]. The importance of cell-mediated immunity to chlamydial infection has been emphasized in a number of studies [3,7].…”