Lack of antigen-specific immune responses in anti-IL-7 receptor alpha chain antibody-treated Peyer's patch-null mice following intestinal immunization with microencapsulated antigen.
Peyer's patches (PP) represent a well-characterized inductive site in gut-associated lymphoid tissue that actively acquires antigens from the intestinal lumen. It was reported that organized PP are not required for antigen-specific IgA responses induced by oral immunization with soluble antigen mixed with the mucosal adjuvant, cholera toxin. However, the role of PP in the induction of mucosal and systemic immune responses remains to be clarified in the case of particulate antigen. Here, we created PP-null mice by treating them with monoclonal anti-IL-7 receptor alpha chain (IL-7 R alpha) antibody during gestation and then immunized with antigen-encapsulated poly-lactic acid (PLA) microspheres. Brisk OVA-specific antibody responses were noted in serum and fecal extracts of normal mice following direct intestinal immunization with OVA in PBS (OVA-PBS) as well as in PLA-microspheres (OVA-MS). Antibody production was similarly elevated in PP-null mice immunized with OVA-PBS via direct injection into the intestinal tract. In contrast, OVA-specific antibody responses were dramatically decreased in both serum and fecal extracts collected from PP-null mice immunized intestinally with OVA-MS. These results were further supported by the number of OVA-specific antibody-forming cells detected in the spleen and intestinal lamina propria. PP deficiency also resulted in the reduction in OVA-specific Th1/Th2 cell responses in the spleen and mesenteric lymph nodes of mice intestinally immunized with OVA-MS. These results suggested that organized PP do, in fact, play a crucial role in the induction of antigen-specific immune responses against ingested particulate antigen.
Kunisawa
Jun
J
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Takahashi
Ichiro
I
Okudaira
Akiko
A
Hiroi
Takachika
T
Katayama
Kazufumi
K
Ariyama
Teruko
T
Tsutsumi
Yasuo
Y
Nakagawa
Shinsaku
S
Kiyono
Hiroshi
H
Mayumi
Tadanori
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology*; D019344:Lactic Acid / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010581:Peyer's Patches / Q000502:physiology*; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage; D020395:Receptors, Interleukin-7 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011091:Polyesters; D011108:Polymers; D020395:Receptors, Interleukin-7; D019344:Lactic Acid; C033616:poly(lactide); D010047:Ovalbumin