Immunological memory in B-cell-deficient mice conveys long-lasting protection against genital tract infection with Chlamydia trachomatis by rapid recruitment of T cells

ABSTRACT CD4+ T-helper type 1 (Th1) responses are essential for the resolution of a primary Chlamydia trachomatis genital tract infection; however, elements of the immune response that function in resistance to reinfection are poorly understood. Defining the mechanisms of immune resistance to reinfection is important because the elements of protective adaptive immunity are distinguished by immunological memory and high-affinity antigen recognition, both of which are crucial to the development of efficacious vaccines. Using in vivo antibody depletion of CD4+ and CD8+ T cells prior to secondary intravaginal challenge, we identified lymphocyte populations that functioned in resistance to secondary chlamydial infection of the genital tract. Depletion of either CD4+ or CD8+ T cells in immune wild-type C57BL/6 mice had a limited effect on resistance to reinfection. However, depletion of CD4+ T cells, but not CD8+ T cells, in immune B-cell-deficient mice profoundly altered the course of secondary infection. CD4-depleted B-cell-deficient mice were unable to resolve a secondary infection, shed high levels of infectious chlamydiae, and did not resolve the infection until 3 to 4 weeks following the discontinuation of anti-CD4 treatment. These findings substantiated a predominant role for CD4+ T cells in host resistance to chlamydial reinfection of the female genital tract and demonstrated that CD8+ T cells are unnecessary for adaptive immune resistance. More importantly, however, this study establishes a previously unrecognized but very significant role for B cells in resistance to chlamydial reinfection and suggests that B cells and CD4+ T cells may function synergistically in providing immunity in this model of chlamydial infection. Whether CD4+ T cells and B cells function independently or dependently is unknown, but definition of those mechanisms is fundamental to understanding optimum protective immunity and to the development of highly efficacious immunotherapies against chlamydial urogenital infections.

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In Situ Analysis of the Evolution of the Primary Immune Response in Murine Chlamydia trachomatis Genital Tract Infection

Infection and Immunity ◽

10.1128/iai.68.5.2870-2879.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2870-2879 ◽

Cited By ~ 75

Author(s):

Sandra G. Morrison ◽

Richard P. Morrison

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Chlamydia Trachomatis ◽

Tract Infection ◽

Inflammatory Response ◽

Genital Tract ◽

Genital Tract Infection ◽

Tnf Α

ABSTRACT Adaptive immune responses contribute to the resolution ofChlamydia trachomatis genital tract infection and protect against reinfection, but our understanding of the mechanisms of those protective responses is incomplete. In this study, we analyzed by in situ immunohistochemistry the progression of the inflammatory and cytokine responses in the genital tracts of mice vaginally infected with C. trachomatis strain mouse pneumonitis. The cellular inflammatory response was characterized by an initial elevation in myeloid cells in the vagina (day 3) and uterine horns (day 7), followed by a marked rise in the number of T cells, predominantly CD4+ cells. CD8+ T cells and CD45R+B cells were also detected but were much less numerous. Perivascular clusters of CD4+ T cells, which resembled clusters of T cells seen in delayed-type hypersensitivity responses, were evident by 2 weeks postinfection. Following the resolution of infection, few CD8+ T cells and CD45R+ B cells remained, whereas numerous CD4+ T cells and perivascular clusters of CD4+ T cells persisted in genital tract tissues. Interleukin-12 (IL-12)- and tumor necrosis factor alpha (TNF-α)-producing cells were observed in vaginal tissue by day 3 of infection and in uterine tissues by day 7. Cells producing IL-4 or IL-10 were absent from vaginal tissues at day 3 of infection but were present in uterine tissues by day 7 and were consistently more numerous than IL-12- and TNF-α-producing cells. Thus, the evolution of the local inflammatory response was characterized by the accumulation of CD4+ T cells into perivascular clusters and the presence of cells secreting both Th1- and Th2-type cytokines. The persistence of CD4+-T-cell clusters long after infection had resolved (day 70) may provide for a readily mobilizable T-cell response by which previously infected animals can quickly respond to and control a secondary infectious challenge.

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Resolution of Secondary Chlamydia trachomatis Genital Tract Infection in Immune Mice with Depletion of Both CD4+ and CD8+ T cells

Infection and Immunity ◽

10.1128/iai.69.4.2643-2649.2001 ◽

2001 ◽

Vol 69 (4) ◽

pp. 2643-2649 ◽

Cited By ~ 76

Author(s):

Sandra G. Morrison ◽

Richard P. Morrison

Keyword(s):

T Cells ◽

B Cells ◽

Chlamydia Trachomatis ◽

Tract Infection ◽

Genital Tract ◽

Delayed Type Hypersensitivity ◽

Predominant Role ◽

Genital Tract Infection

ABSTRACT The essential role of T cells in the resolution of primary murineChlamydia trachomatis genital tract infection is inarguable; however, much less is known about the mechanisms that confer resistance to reinfection. We previously established that CD4+ T cells and B cells contribute importantly to resistance to reinfection. In our current studies, we demonstrate that immune mice concurrently depleted of both CD4+ T cells and CD8+ T cells resisted reinfection as well as immunocompetent wild-type mice. The in vivo depletion of CD4+ and CD8+ T cells resulted in diminished chlamydia-specific delayed-type hypersensitivity responses, but antichlamydial antibody responses were unaffected. Our data indicate that immunity to chlamydial genital tract reinfection does not rely solely upon immune CD4+ or CD8+ T cells and further substantiate a predominant role for additional effector immune responses, such as B cells, in resistance to chlamydial genital tract reinfection.

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