Specific Immunoglobulin-Secreting Human Blood Cells After Peroral Vaccination Against Salmonella typhi

Abstract

Studies on intestinal immunity in animals have suggested that lymphocytes, after sensitization in Peyer's patches and maturation in regional lymph nodes, home via the circulation to the intestinal wall, where they secrete antibodies into the lumen. To detect such homing cells in the blood of human volunteers given oral, attenuated Salmonella typhi vaccine, we used the solid-phase enzyme-linked immunospot assay for S. typhi-specific antibody-secreting cells (ASCs). ASCs were found in eight of 10 individuals after the third postvaccination day, peaked in level on day 7, and were undetectable on day 14. Of the cells secreting specific immunoglobulin, approximately 62% produced IgA, 32% IgM, and 6% IgG. Antibodies could not be demonstrated in serum, saliva, or feces. This technique might give an opportunity to follow the response to antigens entering the body via mucous membranes. It will be of interest to correlate these findings with protection against diseases after peroral vaccination.

Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses.

“…The presence of specific ASC in blood after enteric immunization has also been reported (25,26), an observation supporting the notion of a common mucosal immune system (27). According to this concept, progenitors of B cell immunoblasts recruited at mucosal inductive sites are disseminated via the circulation to their final destination, mainly in the intestinal mucosa, but also in remote mucosa-associated tissues and exocrine glands.…”

Enhancement of the Circulating Antibody Secreting Cell Response in Human Diarrhea by a Human Lactobacillus Strain

“…The total number of ISC (antigen-nonspecific immune response) and sASC (antigen-specific immune response) were determined by the ELlSPOT method, as described previously (8-10). We and others have shown that the number of these lymphocytes in peripheral blood reaches a maximum 6-8 dafter oral administration of antigen (8)(9)(10)(11)(12).…”

“…For th is pu rpose, we used the ELISPOT assay, which measures ISC and sASC amo ng circulating lymphocytes. T hese cells are arrested du ring their maturation cycle in peripheral blood, giving indirect evidence of gut local im m une respo nse (8)(9)(10).…”

Local Immune Response to Upper Urinary Tract Infections in Children

“…This difference in isotype distribution combined with the significantly lower responses observed in children accounts for the fact that the absolute numbers of IgM-ASC did not differ statistically between adults and children, even if a significant difference was found in the total response (IgA-plus IgG-plus IgM-ASC) (P Ͻ 0.003) as well as in IgA-and IgG-ASC responses (P Ͻ 0.003 and P Ͻ 0.002, respectively). In adults, the low IgM-ASC response appears to be a typical feature of the urinary tract (18), since the IgM-ASC response has been shown to be almost as prominent as the IgA-ASC response in adults when the antigen is administered via another mucosal surface, the gastrointestinal tract (13)(14)(15), even after booster immunization (16). Earlier studies have suggested that IgM might have only a minor role in the local immune system of the urinary tract (10), as IgM is rarely, if ever, present in the urine of healthy humans (8).…”

“…The difficulty of getting acute-phase samples at comparable stages of the disease (because the onset of symptoms varies and patients seek medical care after various times) was solved by taking two "acute-phase" samples. In order to catch the peak (or near the peak) of the ASC response, which according to our studies on oral vaccines (13,14) is expected 7 days after antigen exposure, the sampling was carried out as follows. The acute-phase I specimens were collected 1 to 3 days after admission to the hospital, acute-phase II specimens were collected 1 week later, and convalescentphase samples were collected 3 to 7 weeks after the onset of the disease.…”