Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses.
Mucosal immunoglobulin A (IgA) responses are often associated with Th2-type cells and derived cytokines, and interleukin-4 (IL-4) knockout (IL-4-/-) mice with impaired Th2 cells respond poorly to oral antigens. However, we have noted that IL-4-/- mice have normal mucosal IgA levels, which led us to query whether different oral delivery systems could elicit mucosal immunity. Two oral regimens were used: (i) a live recombinant Salmonella strain which expresses fragment C (ToxC) of tetanus toxin, and (ii) soluble tetanus toxoid (TT) with cholera toxin (CT) as an adjuvant. Oral immunization of IL-4-/- mice with recombinant Salmonella vaccine expressing ToxC induced brisk mucosal IgA and serum IgG (mainly IgG2a) anti-TT antibody responses. TT-specific CD4+ T cells from spleen or Peyer's patches produced gamma interferon, indicative of Th1 responses; however, IL-6 and IL-10 were also seen. Oral immunization of IL-4-/- mice with TT and CT induced weak mucosal IgA to TT; however, brisk IgA anti-CT-B responses and CT-B-specific CD4+ T cells producing IL-6 and IL-10 were also noted. These results show that although IL-4-dependent antibody responses are impaired, mucosal IgA responses are induced in IL-4-/- mice. These result suggest that certain cytokines, i.e., IL-6 and IL-10 from Th2-type cells, play an important compensatory role in the induction and regulation of mucosal IgA responses.
Okahashi
N
N
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
Yamamoto
M
M
Vancott
J L
JL
Chatfield
S N
SN
Roberts
M
M
Bluethmann
H
H
Hiroi
T
T
Kiyono
H
H
McGhee
J R
JR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics* / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012475:Salmonella / Q000276:immunology*; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D013744:Tetanus Toxin; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D002772:Cholera Toxin