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Infection and Immunity, December 2003, p. 6835-6843, Vol. 71, No. 12
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.12.6835-6843.2003
Copyright © 2003, American
Society for
Microbiology. All Rights Reserved.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,1 The Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021,2 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191043
Received 25 June 2003/ Returned for modification 17 August 2003/ Accepted 18 September 2003
Protective
immunity in mice to the infective third-stage larvae (L3) of
Strongyloides stercoralis was shown to be dependent on
immunoglobulin M (IgM), complement activation, and granulocytes. The
objectives of the present study were to determine whether IgG was also
a protective antibody isotype and to define the specificity and the
mechanism by which IgG functions. Purified IgG recovered from mice 3
weeks after a booster immunization with live L3 was shown to transfer
high levels of protective immunity to naïve mice. IgG
transferred into mice treated to block complement activation or to
eliminate granulocytes failed to kill the challenge larvae. Transfer of
immune IgG into IL-5 knockout (KO) mice, which are deficient in
eosinophils, resulted in larval attrition, while transfer into
FcR
KO mice did not result in larval killing. These findings
suggest that IgG from mice immunized with live L3 requires complement
activation and neutrophils for killing of L3 through an
antibody-dependent cellular cytotoxicity (ADCC) mechanism.
This is in contrast to the results of investigations using IgM from
mice immunized with live L3 and IgG from mice immunized with larval
antigens soluble in deoxycholate in which protective immunity was shown
to be ADCC independent. Western blot analyses with immune IgM and IgG
identified few antigens recognized by all protective antibody isotypes.
Results from immunoelectron microscopy demonstrated that the protective
antibodies bound to different regions in the L3. It was therefore
concluded that while IgM and IgG antibodies are both protective against
larval S. stercoralis, they recognize different antigens and
utilize different killing
mechanisms.
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