Infection and Immunity · 2000 · 249 citations · 58 references
Life SciencesImmunologyInfectious DiseasesAdaptive ImmunityImmunology Of Infectious DiseasesMucosal ImmunologyAdaptive Immune ResponsesB-cell ResponsesCell-mediated ImmunityHelper T Cell SubsetsHumoral ImmunityProtective ImmunityCd4 Positive T Cell ResponsesCd4 Positive T CellsCd4+ T Helper Cell ResponsesCd8 Positive T Cell ResponsesProtective Immunological MemoryT-cell Immune ResponsesT-cell Mediated Responses
CD4⁺ Th1 responses are required to clear primary Chlamydia trachomatis genital infections, yet the adaptive immune mechanisms that prevent reinfection remain poorly defined and are critical for vaccine design. The study aimed to determine whether CD4⁺ T cells and B cells act independently or synergistically to protect against chlamydial reinfection. In vivo depletion of CD4⁺ and CD8⁺ T cells before a secondary intravaginal challenge was used to identify the lymphocyte populations mediating resistance to reinfection. Depletion of CD4⁺ T cells in B‑cell‑deficient mice abolished clearance of secondary infection, whereas CD8⁺ T cell depletion had little effect, revealing that CD4⁺ T cells and B cells cooperate to confer immunity while CD8⁺ T cells are dispensable.
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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Genome Sequence of an Obligate Intracellular Pathogen of Humans: <i>Chlamydia trachomatis</i>
Richard S. Stephens, Sue Kalman, C. J. Lammel et al. · Science · 1998 · 1.6K citations
Robert Morrison, Karen Feilzer, Daniel B. Tumas · Infection and Immunity · 1995 · 335 citations · Full text