Genital-associated lymphoid tissue in female non-human primates.
We investigated genital-associated lymphoid tissue (GENALT) in non-human primates (macaques), by augmenting vaginal with oral immunization. The vaccine was a recombinant particulate SIV antigen (p27:Ty-VLP), linked to CT-B, and administered into the vagina by a paediatric naso-gastric tube and into the stomach by a gastric tube. Oro-vaginal or vagino-oral sequence of immunization elicited specific CD4+ T cell proliferative responses to p27 antigen in the genital lymph nodes and the spleen but not in unrelated lymph nodes. CD4+ T cells reconstituted with B cells and macrophages from the genital lymph nodes induced specific IgA and to a lesser extent IgG anti-p27 antibodies. However, the corresponding splenic cells induced greater IgG than IgA antibody synthesis. Intramuscular immunization primed splenic but not genital lymph node cells, and induced CD4+ T cell proliferative responses and predominantly B cell IgG antibody synthesis. Finding primed B and T cells in the genital lymph nodes after augmenting vaginal by oral immunization provides experimental evidence for GENALT in non-human primates. This primate model of vaginal immunization suggests 3 levels of specific immunity: (1) secretory IgA (and IgG) in the cervico-vaginal mucosal epithelium; (2) primed CD4+ T cells and B cells in the genital lymph nodes and the spleen; and (3) circulating CD4+ T cells, B cells and IgG and IgA antibodies specific to the immunizing antigen.
Department of Immunology, UMDS of Guy's Hospital, London, United Kingdom.
T
T
Lehner
C
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Panagiotidi
L A
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Bergmeier
L
L
Tao
R
R
Brookes
A
A
Gearing
S
S
Adams
D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D002584:Cervix Uteri / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008211:Lymphocyte Cooperation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D018626:Retroelements / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology; D014621:Vagina / Q000276:immunology*; D014734:Vibrio cholerae / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018626:Retroelements; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D002772:Cholera Toxin