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Infection and Immunity, September 1998, p. 4030-4035, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Route of Infection That Induces a High Intensity of Gamma
Interferon-Secreting T Cells in the Genital Tract Produces Optimal
Protection against Chlamydia trachomatis Infection in
Mice
Joseph U.
Igietseme,1,*
Ijindah M.
Uriri,1
Shantha N.
Kumar,1
Godwin A.
Ananaba,2
Omegbhai O.
Ojior,1
Inua A.
Momodu,1
Debra H.
Candal,3 and
Carolyn M.
Black3
Department of Microbiology and Immunology,
Morehouse School of Medicine, Atlanta, Georgia
303101;
Department of Biology,
Spelman College, Atlanta, Georgia 303142; and
National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, Georgia
303333
Received 19 March 1998/Returned for modification 5 May
1998/Accepted 10 June 1998
The induction of local T helper type 1 (Th1)-mediated cellular
immunity is crucial for resistance of mice to genital infection by the
obligate intracellular bacterium Chlamydia trachomatis. We
tested the hypothesis that the route of immunization that elicits relatively high numbers of chlamydia-specific, gamma interferon (IFN-
)-secreting T lymphocytes (ISTLs) in the genital tract
would induce optimal protective immunity against reinfection.
Female BALB/c mice were infected intravaginally (i.v.), intranasally (i.n.), orally (p.o.), or subcutaneously (s.c.) with C. trachomatis. At days 7, 14, 21, and 28 postinfection, T cells
isolated from the genital tract tissues were restimulated with
chlamydial antigen in vitro, and the amounts of IFN-
induced were
measured by a sandwiched enzyme-linked immunosorbent assay method. At
day 7 postinfection, i.n.- and i.v.-immunized mice had high levels of chlamydia-specific ISTLs in their genital tracts (203.58 ± 68.1 and 225.5 ± 12.1 pg/ml, respectively). However, there were no detectable ISTLs in the genital tracts of p.o.- or s.c.-infected mice.
When preinfected mice were challenged i.v. 70 days later, animals
preexposed by the i.n. route were highly resistant to reinfection, with
greatly reduced chlamydial burden, and suffered an attenuated infection
that resolved by day 6 postchallenge. Animals preexposed by the i.v.
route were modestly protected, whereas p.o. and s.c. groups were
indistinguishable in this regard from control mice. The resistance of
i.n.-immunized mice (and to some extent the i.v.-exposed mice) to
reinfection was associated with early appearance (within 24 h) of
high levels of genital ISTLs compared with mice preinfected by other
routes. Furthermore, although i.n. and i.v.-immunized mice had
comparable levels of chlamydia-specific immunoglobulin A (IgA)
antibodies in their vaginal washes, the levels of IgG2a were four-
sixfold higher in i.n.-immunized mice than in any of the other groups.
The results suggested that immunization routes that foster rapid
induction of vigorous genital mucosal cell-mediated immune (CMI)
effectors (e.g., IFN-
), the CMI-associated humoral effector, IgG2a,
and to some extent secretory IgA produce protective immunity
against chlamydial genital infection. Therefore, i.n. immunization is a
potential delivery route of choice in the development of a vaccine against Chlamydia.
*
Corresponding author. Mailing address: Morehouse School
of Medicine, Department of Microbiology and Immunology, 720 Westview Dr., SW, Atlanta, GA 30310. Phone: (404) 752-1596. Fax: (404) 752-1179. E-mail: igietsj{at}msm.edu.
Infection and Immunity, September 1998, p. 4030-4035, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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