Affiliation:
1. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164,1 and
2. Department of Parasitology, Kimron Veterinary Institute, Bet-Dagan, Israel2
Abstract
ABSTRACT
Protective immunity against the ehrlichial pathogen
Anaplasma marginale
has been hypothesized to require induction of immunoglobulin G2 (IgG2) antibody against outer membrane protein epitopes and coordinated activation of macrophages for phagocytosis and killing. In the present study, cell-mediated immune responses, including induction of IgG isotype switching, were characterized in calves immunized with purified outer membranes of the Florida strain of
A. marginale
. Importantly, these calves were subsequently shown to be protected upon experimental challenge with the Florida strain, and calves which developed the highest IgG2 titers were completely protected against infection. Peripheral blood mononuclear cells (PBMC) obtained after immunization proliferated strongly in response to both whole
A. marginale
homogenates and purified outer membranes, and this responsiveness persisted until the time of challenge. Responding cells were shown to be CD4
+
T cells, and CD4
+
T-cell lines cultured for 2 to 4 weeks also proliferated specifically in response to
A. marginale
and produced high titers of gamma interferon. The helper T-cell response included recognition of conserved epitopes, as PBMC proliferation was stimulated by the homologous Florida strain, four genetically distinct
A. marginale
strains, and
Anaplasma ovis
. The outer membrane proteins stimulating the PBMC responses in protected calves included major surface proteins (MSPs) MSP-1, MSP-2, and MSP-3, which were previously shown to induce partial protection against infection. These studies demonstrate, for the first time, potent helper T-cell responses in cattle protectively immunized with outer membranes against
A. marginale
challenge and identify three MSPs that are recognized by immune T cells. These experiments provide the basis for subsequent identification of the helper T-cell epitopes on MSP-1, MSP-2, and MSP-3 that are needed to evoke anamnestic antibody and effector T-cell responses elicited by protein or nucleic acid immunization.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
125 articles.
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