title: Immunity to murine Chlamydia trachomatis genital tract reinfection involves B cells and CD4(+) T cells but not CD8(+) 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.
authors.affiliation: Department of Microbiology, Montana State University, Bozeman, Montana 59717, USA. morrison@montana.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Morrison
authors.forename: H
authors.initials: H
authors.lastname: Su
authors.forename: H D
authors.initials: HD
authors.lastname: Caldwell
authors.forename: R P
authors.initials: RP
authors.lastname: Morrison
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012008:Recurrence