Immunology 1990 70 121-125
Secretory immune responses in mouse vaginal fluid after pelvic, parenteral or vaginal immunization M. A. THAPAR, E. L. PARR & M. B. PARR Department of Anatomy, School of Medicine, Southern Illinois University, Carbondale, Illinois, U.S.A.
Acceptedfor publication 15 January 1990
SUMMARY Intravaginal immunization causes IgA responses in vaginal fluid, but so far lymphoid nodules in mouse vaginal mucosa have not been detected. The present study was therefore designed to test the hypothesis that IgA responses in the female reproductive tract may be generated in the regional iliac lymph nodes. Two, non-mucosal sites were identified in the female mouse pelvis, the subserous and presacral spaces, from which lymph drains mainly to the iliac nodes. Immunization at these pelvic sites with horse ferritin adsorbed to aluminum hydroxide (AH) caused much higher IgA and IgG titres in vaginal fluid than intravaginal immunization; moreover, the pelvic immunizations caused significantly higher and better sustained IgA titres in vaginal fluid than subcutaneous immunization near the scapulae or in the perineum, while IgG titres in vaginal fluid were similar in these groups. Additional mice were immunized with ferritin subcutaneously near the scapulae or in the presacral pelvic space using dimethyl dioctadecyl ammonium bromide (DDA), AH plus muramyl dipeptide, or the Ribi adjuvant system as adjuvants. Pelvic immunization caused higher IgA titres in vaginal fluid than subcutaneous immunization in each case. The IgA response stimulated by DDA was similar to that produced by AH but higher than the responses caused by the other two adjuvants, while IgG titres were similar with all four adjuvants in both sites. The results suggest that non-mucosal, pelvic immunization is particularly effective in stimulating IgA responses in the female reproductive tract. The observation is consistent with the possibility that the iliac lymph nodes may play a role in the development of IgA responses in the reproductive tract.
Previous reports have suggested that IgA responses in the respiratory tract may be generated, at least in part, in the regional mediastinal lymph nodes (Spencer, Guyure & Hall, 1983; Hall & Spencer, 1984). If the regional lymph nodes are important for IgA responses in the female reproductive tract, then immunization at non-mucosal sites in the pelvis from which lymph drains to the regional nodes should stimulate specific IgA secretion in the vagina. The present study was designed to test this prediction. It has been demonstrated previously that lymph from the mouse vagina drains to the iliac lymph nodes (Parr & Parr, 1990). Here two, non-mucosal sites are identified in the female mouse pelvis from which lymph drains mainly to these nodes, and immunization at both sites caused significantly higher IgA titres in vaginal fluid than immunization at other sites.
INTRODUCTION Immunoglobulins are secreted into the lumen of the female reproductive tract, where they may play a role in protection against mucosal infections (Schumacher, 1980). Both IgA and IgG are present in the secretions, but IgA is of particular interest because at other mucosal sites it is more effective than IgG in preventing bacterial infections (Fubara & Freter, 1973; Bessen & Fischetti, 1988). It is well known that secretory IgA responses can be generated in mucosal lymphoid nodules, such as Peyer's patches, and that local application of antigen at the mucosal surface is often an effective way to elicit such responses (PhilipsQuagliata & Lamm, 1988). In the female reproductive tract, local application of antigen to the vaginal mucosa via tampons caused specific IgA secretion in mouse vaginal fluid, but extensive histological examination failed to reveal lymphoid nodules in vaginal mucosa (Parr, Parr & Thapar, 1988). It is therefore not clear where IgA responses are generated after intravaginal immunization.
MATERIALS AND METHODS Animals Female ICR mice, 60-100 days old, were purchased from Sasco Inc., Omaha, NE and housed next to males of the same strain to induce cycling.
Correspondence: Ms M. A. Thapar, Dept. of Anatomy, School of Medicine, Southern Illinois University, Carbondale, IL 62901-6503, U.S.A.
121
122
M. A. Thapar, E.L. Parr & M.B. Parr (a)
Z Peritoneum
Subserous space Pelvic diaphragm and
Urethra
Pubic bane
perineal membrane
Secretory immune responses in mouse vaginal fluid after pelvic, parenteral or vaginal immunization M. A. THAPAR, E. L. PARR & M. B. PARR Department of Anatomy, School of Medicine, Southern Illinois University, Carbondale, Illinois, U.S.A.
Acceptedfor publication 15 January 1990
SUMMARY Intravaginal immunization causes IgA responses in vaginal fluid, but so far lymphoid nodules in mouse vaginal mucosa have not been detected. The present study was therefore designed to test the hypothesis that IgA responses in the female reproductive tract may be generated in the regional iliac lymph nodes. Two, non-mucosal sites were identified in the female mouse pelvis, the subserous and presacral spaces, from which lymph drains mainly to the iliac nodes. Immunization at these pelvic sites with horse ferritin adsorbed to aluminum hydroxide (AH) caused much higher IgA and IgG titres in vaginal fluid than intravaginal immunization; moreover, the pelvic immunizations caused significantly higher and better sustained IgA titres in vaginal fluid than subcutaneous immunization near the scapulae or in the perineum, while IgG titres in vaginal fluid were similar in these groups. Additional mice were immunized with ferritin subcutaneously near the scapulae or in the presacral pelvic space using dimethyl dioctadecyl ammonium bromide (DDA), AH plus muramyl dipeptide, or the Ribi adjuvant system as adjuvants. Pelvic immunization caused higher IgA titres in vaginal fluid than subcutaneous immunization in each case. The IgA response stimulated by DDA was similar to that produced by AH but higher than the responses caused by the other two adjuvants, while IgG titres were similar with all four adjuvants in both sites. The results suggest that non-mucosal, pelvic immunization is particularly effective in stimulating IgA responses in the female reproductive tract. The observation is consistent with the possibility that the iliac lymph nodes may play a role in the development of IgA responses in the reproductive tract.
Previous reports have suggested that IgA responses in the respiratory tract may be generated, at least in part, in the regional mediastinal lymph nodes (Spencer, Guyure & Hall, 1983; Hall & Spencer, 1984). If the regional lymph nodes are important for IgA responses in the female reproductive tract, then immunization at non-mucosal sites in the pelvis from which lymph drains to the regional nodes should stimulate specific IgA secretion in the vagina. The present study was designed to test this prediction. It has been demonstrated previously that lymph from the mouse vagina drains to the iliac lymph nodes (Parr & Parr, 1990). Here two, non-mucosal sites are identified in the female mouse pelvis from which lymph drains mainly to these nodes, and immunization at both sites caused significantly higher IgA titres in vaginal fluid than immunization at other sites.
INTRODUCTION Immunoglobulins are secreted into the lumen of the female reproductive tract, where they may play a role in protection against mucosal infections (Schumacher, 1980). Both IgA and IgG are present in the secretions, but IgA is of particular interest because at other mucosal sites it is more effective than IgG in preventing bacterial infections (Fubara & Freter, 1973; Bessen & Fischetti, 1988). It is well known that secretory IgA responses can be generated in mucosal lymphoid nodules, such as Peyer's patches, and that local application of antigen at the mucosal surface is often an effective way to elicit such responses (PhilipsQuagliata & Lamm, 1988). In the female reproductive tract, local application of antigen to the vaginal mucosa via tampons caused specific IgA secretion in mouse vaginal fluid, but extensive histological examination failed to reveal lymphoid nodules in vaginal mucosa (Parr, Parr & Thapar, 1988). It is therefore not clear where IgA responses are generated after intravaginal immunization.
MATERIALS AND METHODS Animals Female ICR mice, 60-100 days old, were purchased from Sasco Inc., Omaha, NE and housed next to males of the same strain to induce cycling.
Correspondence: Ms M. A. Thapar, Dept. of Anatomy, School of Medicine, Southern Illinois University, Carbondale, IL 62901-6503, U.S.A.
121
122
M. A. Thapar, E.L. Parr & M.B. Parr (a)
Z Peritoneum
Subserous space Pelvic diaphragm and
Urethra
Pubic bane
perineal membrane
