Anti-Cholera Toxin Iga-, Igg- And Igm-Secreting Cells in Various Rat Lymphoid Tissues After Repeated Intestinal or Parenteral Immunizations

Abstract

Single antibody-secreting spot-forming cells (SFC) of the 3 main isotypes were counted in lymphoid cells from the gut lamina propria (LP), Peyer's patches (PP), mesenteric nodes (MN) and spleen (SP) of rats immunized 2-6 times intraduodenally (ID) or intraperitoneally (IP) with cholera toxin (CT). Responses for all isotypes peaked in all tissues after 4 ID- or IP-immunizations at much larger values than previously reported, and significantly decreased thereafter, except in LP and PP after IP-injections, where IgA- or IgG-SFC, but not IgM-SFC, only appeared or increased after 6 IP-doses. The highest IgA-SFC numbers (17% of tested cells) were in LP after 4 ID-doses. The isotype ratio was IgA greater than IgG greater than IgM in LP and PP after ID-injections, but IgG greater than IgA greater than IgM in MN and SP after both ID- and IP-routes. The isotype dispersion was much larger in LP and PP than in MN and SP. Our data show that at least 4 IP CT-doses were required to only elicit a few IgG- and almost no IgA-SFC in LP and PP, outlining the need for intestinal CT-immunizations to induce strong mucosal IgA-SFC responses. We also show good systemic responses elicited both by enteral and parenteral routes, and the small contribution of PP in total SFC, particularly after parenteral immunizations.

Protection of rat intestine against cholera toxin challenge by monoclonal anti-idiotypic antibody immunization via enteral and parenteral routes

“…Clearly, it would be of major interest to unambiguously correlate local intestinal IgA anti-CT Ab content (rather than just in bile) and/or numbers of IgA Ab-secreting cells in the wall of the challenged loops with the degree of protection. Such studies are now under way in our group (39), as well as studies of various amounts of MAb2, their liposomal entrapment, and their anti-CT priming potential and/or memoryevoking capacity. The anti-caries anti-id immunization by Jackson et al (11) was the first published attempt at anti-id vaccination by stimulation of the intestinal immune system, obviously a major concern since mucosae are the natural port of entry of most pathogens.…”

Characterization and utility of novel monoclonal antibodies to cholera toxin B subunit

“…[2][3][4] CTB has been produced in various recombinant expression platforms as model vaccines, [5][6][7][8] as it induces a strong immune response characterized by neutralizing antibodies to the CTX via oral administration. 9,10 CTB has also been used as a molecular scaffold for immunization 11,12 and for induction of peripheral (oral) immunological tolerance to suppress allergies and various autoimmune disorders such as experimental autoimmune encephalitis (EAE), diabetes, arthritis and uveitis in an antigen-specific manner. [13][14][15][16][17] CTB is considered a mucosal immunomodulator that induces a strong mucosal IgA response while it seems to suppress systemic T helper (T H 1, T H 2 and T H 17) responses through the induction of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β)-mediated regulatory T (Treg) induction and suppression of proinflammatory IL-6, 18 although the exact mechanism behind such immunomodulation remains elusive.…”

Characterization and utility of novel monoclonal antibodies to cholera toxin B subunit

“…[2][3][4] CTB has been produced in various recombinant expression platforms as model vaccines, [5][6][7][8] as it induces a strong immune response characterized by neutralizing antibodies to the CTX via oral administration. 9,10 CTB has also been used as a molecular scaffold for immunization 11,12 and for induction of peripheral (oral) immunological tolerance to suppress allergies and various autoimmune disorders such as experimental autoimmune encephalitis (EAE), diabetes, arthritis and uveitis in an antigen-speci c manner. [13][14][15][16][17] CTB is considered a mucosal immunomodulator that induces a strong mucosal IgA response while it seems to suppress systemic T helper (T H 1, T H 2 and T H 17) responses through the induction of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β)-mediated regulatory T (Treg) cell induction and suppression of proin ammatory IL-6, 18 although the exact mechanism behind such immunomodulation remains elusive.…”