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,§
*
Department of Clinical Pathology, Nihon University School of Dentistry at Matsudo, Chiba, Japan;
Biogen Institute, Cambridge, MA 02142;
Immunobiology Vaccine Center and Departments of Oral Biology and Microbiology, University of Alabama Medical Center, Birmingham, AL 35294;
§
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and
¶
F. Hoffmann La-Roche, Basel, Switzerland
The progeny of mice treated with lymphotoxin (LT)-ß receptor
(LTßR) and Ig (LTßR-Ig) lack Peyer’s patches but not mesenteric
lymph nodes (MLN). In this study, we used this approach to determine
the importance of Peyer’s patches for induction of mucosal IgA Ab
responses in the murine gastrointestinal tract. Immunohistochemical
analysis revealed that LTßR-Ig-treated, Peyer’s patch null (PP null)
mice possessed significant numbers of IgA-positive (IgA+)
plasma cells in the intestinal lamina propria. Further, oral
immunization of PP null mice with OVA plus cholera toxin as mucosal
adjuvant resulted in Ag-specific mucosal IgA and serum IgG Ab
responses. OVA-specific CD4+ T cells of the Th2 type were
induced in MLN and spleen of PP null mice. In contrast, when TNF and
LT-
double knockout (TNF/LT--/-) mice, which lack
both Peyer’s patches and MLN, were orally immunized with OVA plus
cholera toxin, neither mucosal IgA nor serum IgG anti-OVA Abs were
induced. On the other hand, LTßR-Ig- and TNF receptor 55-Ig-treated
normal adult mice elicited OVA- and cholera toxin B subunit-specific
mucosal IgA responses, indicating that both LT-ß and TNF/LT-
pathways do not contribute for class switching for IgA Ab responses.
These results show that the MLN plays a more important role than had
been appreciated until now for the induction of both mucosal and
systemic Ab responses after oral immunization. Further, organized
Peyer’s patches are not a strict requirement for induction of mucosal
IgA Ab responses in the gastrointestinal tract.
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