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Biomedical subjects

J Mestecky

Publications and source records attributed to J Mestecky.

At least 73 records · Page 4Linked to original sources
PubMed1995

T lymphocytes infiltrating advanced grades of cervical neoplasia. CD8-positive cells are recruited to invasion.

BACKGROUND: Impaired cellular immunity appears to be a risk factor for progression of cervical neoplasia, but the immunobiology of neoplastic progression is poorly understood. The objective of this study was to characterize the subpopulations of T lymphocytes that infiltrate various grades of cervical neoplasia including metaplasia to invasive cancer in immunocompetent women. METHOD: In 65 patients with a spectrum of cervical disease ranging from normal cytology to carcinoma, the relative proportions of total T lymphocytes and CD4- or CD8-expressing (helper or cytotoxic) T lymphocyte subsets were determined by immunohistochemistry. RESULTS: When the invasive carcinoma stromal infiltrate was compared with the infiltrate of preinvasive lesions, the numbers of total T cells and the CD8-positive subset increased significantly in the invasive cancers (P < 0.005). Although immunocyte infiltrates were highly concentrated in focal clusters beneath the preinvasive squamous lesions, the CD8-positive immunocytes diffusely infiltrated the invading tumor. CONCLUSIONS: The CD8-positive T cell infiltrate far exceeded the CD4-positive cells in the invasive, but not in the preinvasive lesions, a finding that suggests that CD8 cells are recruited preferentially to cervical lesions with progression to invasion.

CD4-Positive T-Lymphocytes↗
PubMed1995

Human immune responses to influenza virus vaccines administered by systemic or mucosal routes.

Healthy adult volunteers were immunized by parenteral or oral routes with trivalent inactivated influenza vaccine (A/Chile/1/83 (H1N1), A/Mississippi/1/85 (H3N2), and B/Ann Arbor/1/86), or intranasally with live attenuated, cold-adapted influenza type A/Texas/1/85 (H1N1) reassortant virus. In all volunteers, cells spontaneously secreting IgA, IgG or IgM antibodies specific to influenza virus were detected in peripheral blood on days 6-13 after immunization, and specific IgA, IgG and IgM antibodies to influenza vaccine were measured in sera and external secretions (saliva and nasal lavage). Following systemic immunization, a raise in specific antibodies of all isotypes was observed in sera beginning on day 13. Although small variations in IgA and IgM antibodies in saliva and nasal lavages were detected, antigen-specific IgG significantly increased between days 13 and 27. Intranasal administration of attenuated virus induced IgA and IgG antibodies in serum as well as in secretions. Serum antibodies were not substantially influenced by oral immunization, only a small increase in all isotypes was observed in volunteers' sera 21 days after ingestion of vaccine. However, in secretions, antigen-specific IgA and IgG responses were detected one week after immunization and reached a peak response on day 20. These studies show that different routes of immunization can be effective for the induction of specific antibodies, and support the concept of the common mucosal immune system in humans by demonstrating that the oral or intranasal administration of antigen-induced specific antibodies of IgA isotype in external secretions, preceded by the transient appearance in peripheral blood of specific antibody-producing cells.

Administration, Intranasal↗
PubMed1995

Intestinal immune function is unaffected by parenteral nutrition in man.

BACKGROUND: Animal studies have demonstrated intestinal immunoglobulin production is decreased when luminal nutrition is withheld and nutrition is provided solely on the basis of total parenteral nutrition (TPN). METHODS: Eight normal volunteers were hospitalized in the Clinical Research Center for three weeks. The subjects received TPN as an exclusive means of nutritional support for 14 days followed by 5 days of enteral feeding with either standard or a glutamine- and arginine-supplemented formula in which the protein source was primarily free amino acids and peptides. Endoscopic jejunal biopsies obtained before and after TPN and following enteral refeeding were evaluated by immunofluorescence for the number of IgA, IgM and IgG-producing cells; T and B cells as well as intraepithelial and lamina propria lymphocytes were also counted. Serum immunoglobulins and the molecular forms of serum IgA were determined at the same intervals. RESULTS: The number of intestinal IgA-, IgM- and IgG-producing cells was unaffected by TPN (676 +/- 58 vs. 643 +/- 38, 101 +/- 14 vs. 98 +/- 18, 10 +/- 1 vs. 11 +/- 2 per low power field). The total number of intestinal lymphocytes, and CD3+ lymphocytes in the intraepithelial area was unaffected by TPN (10.4 +/- 0.4 vs. 10.2 +/- 1.3, 7.3 +/- 0.8 vs. 8.6 +/- 1.6 per 100 epithelial cells). Similarly, the total number of lymphocytes and CD3+ lymphocytes in the intestinal lamina propria was unaffected by TPN (4.4 +/- 0.2 vs. 6.2 +/- 0.8, 3.3 +/- 0.7 vs. 4.5 +/- 0.8). A small, but statistically significant increase in serum IgA and IgM was seen with TPN 314 +/- 11 vs. 342 +/- 16 mg/dL and 154 +/- 25 vs. 226 +/- 47 mg/dL, although IgG remained unchanged (1262 +/- 69 vs. 1207 +/- 57 mg/dL). The proportion of polymeric and monomeric serum IgA remained unchanged after TPN (19.2 vs. 22.1% polymeric). CONCLUSIONS: The use of TPN is not associated with intestinal immune dysfunction in man. A small, but statistically significant increase in serum IgM, and a borderline statistically significant increase in serum IgM were associated with TPN. The etiology and clinical significance of these observations is unclear.

Adult↗
PubMed1995

Normal uterine cervix: characterization of isolated lymphocyte phenotypes and immunoglobulin secretion.

PROBLEM: Isolation of viable cervical lymphocyte populations and characterization of their function in healthy tissue is necessary to understand immunity in the genital tract. METHODS: Normal, cervical tissue was digested using a multi-enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of 90-98% were isolated from normal cervical tissue. FACS analysis determined that B lymphocytes were the predominant cell type in normal cervical tissue representing a significantly higher percentage than that found in peripheral blood (P = 0.015). T lymphocytes and NK cells represented a significantly lower percentage than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The largest percentage of immunoglobulin secreting cells isolated were secreting IgG followed by IgA. A limited number of IgM secreting cells were detected. IgA2 secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma cells. CONCLUSION: These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.

Adult↗
PubMed1995

Ig-secreting and interferon-gamma-producing cells in mice mucosally immunized with influenza virus.

1. Oral immunization of mice with influenza virus type A/Udorn, induced antigen-specific IgA antibodies in external secretions (e.g., saliva and fecal extract). 2. Increased numbers of antigen-specific IgA spot-forming cells (SFC) were seen in mononuclear cells isolated from IgA-effector tissues (e.g., SG) of mice orally-immunized with influenza virus. 3. Following oral or systemic immunization of mice, IFN gamma-secreting cells (Th1 type) displayed a characteristic pattern of distribution which was related to the route of immunization.

Administration, Oral↗
PubMed1995

Antisperm antibodies in infertile women: subclass distribution of immunoglobulin (Ig) A antibodies and removal of IgA sperm-bound antibodies with a specific IgA1 protease.

OBJECTIVE: To determine the immunoglobulin (Ig) A subclass distribution of antibodies in the serum and cervical mucus (CM) of infertile women and to evaluate the effect of an IgA1 protease on the removal of sperm-bound antibodies. METHODS: Twenty infertile women with antisperm antibodies in serum (n = 10) or in CM (n = 10) were recruited for this study. Monoclonal antibodies to human IgA1 and IgA2 were conjugated to immunobeads and the IgA subclass distribution of antisperm antibodies was determined for positive serum and CM samples. The effect of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm-bound antibodies was evaluated by immunobead binding. RESULTS: In serum, IgA1 subclass antisperm antibodies predominated (89%) when compared to IgA2 (11%). In CM IgA1 accounted for 62% and IgA2 accounted for 38% of the total IgA antisperm antibodies. Enzyme treatment was able to reduce dramatically the amount of serum IgA antibodies bound to sperm from 88% to 10%. Similarly, a significant reduction in CM antisperm antibodies was observed after enzymatic treatment with no loss in sperm motility. CONCLUSION: Cervical mucus antisperm antibodies have a higher proportion of IgA2 subclass suggesting a local production of IgA. Specific IgA1 protease treatment is capable of reducing the amount of immunobead-detectable IgA on sperm. Hamster sperm penetration assays are ongoing to determine if this treatment might improve sperm penetration rates with antibody positive sperm.

Antibodies↗