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Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals.
Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals.
- Source :
-
AIDS (London, England) [AIDS] 1995 Jul; Vol. 9 (7), pp. 695-700. - Publication Year :
- 1995
-
Abstract
- Objective: To examine possible changes in mucosal B-cell activation status.<br />Design: To examine the frequency and isotype distribution of total and HIV-specific antibody-secreting cells (ASC) in the intestinal mucosa of HIV-infected individuals.<br />Methods: Mucosal lymphocytes were obtained by enzymatic treatment of duodenal pinch biopsies and the numbers of ASC were assayed with the enzyme-linked immunospot technique.<br />Results: High numbers of HIV-specific ASC were found in the intestine of all HIV-infected individuals despite low levels of HIV-specific blood ASC. All HIV-infected individuals had large numbers of intestinal immunoglobulin (Ig) A-ASC against the HIV envelope glycoprotein gp160. Eight out of nine patients also had HIV gp160-specific intestinal IgG-ASC. These HIV-specific ASC were detected irrespective of disease stage, route of infection, or levels of circulating CD4+ T cells. HIV-specific ASC were found in peripheral blood from patients with CD4+ T cells > or = 100 x 10(6)/l blood, but in none of three patients with low CD4+ T-cell counts. The frequencies of virus-specific ASC in the blood were on average 100-fold lower than that observed within the intestinal mucosa. Mucosal polyclonal B-cell activation was evident in HIV-infected individuals, as documented by significantly elevated numbers of Ig-secreting cells (ISC) in all three major Ig classes; on average, seven-, five- and 20-fold numbers of IgA, IgG and IgM-ISC compared with healthy controls. Furthermore, substantial numbers of ASC reacting with unrelated antigens such as dog albumin and keyhole limpet haemocyanin were detected in HIV-infected patients. Interestingly, patients with CD4+ T cells < 100 x 10(6)/l blood displayed large numbers of HIV-specific intestinal ASC even though total numbers of ISC, including ASC reactive to unrelated antigens, were decreased.<br />Conclusions: The large numbers of virus-specific ASC found in the intestine of HIV-infected individuals may be a consequence of local replication of HIV-1 resulting in a continuous antigen stimulation. The persistence of strong intestinal anti-HIV responses even at late stages of disease suggest that the mucosal B-cell responses are functionally intact throughout the disease. Furthermore, these results suggest that there is no correlation between HIV-specific ASC numbers and polyclonal B-cell activation. These observations indicate that intestinal B-cell activation is profoundly disregulated in HIV-infected individuals.
- Subjects :
- Antibody Formation
Antibody-Producing Cells pathology
Antibody-Producing Cells virology
B-Lymphocytes pathology
B-Lymphocytes virology
Female
Gene Products, env immunology
HIV Envelope Protein gp160
HIV Infections pathology
HIV Infections virology
Humans
Intestinal Mucosa pathology
Intestinal Mucosa virology
Male
Protein Precursors immunology
Antibodies, Viral analysis
Antibody-Producing Cells immunology
B-Lymphocytes immunology
HIV Infections immunology
Intestinal Mucosa immunology
Lymphocyte Activation
Subjects
Details
- Language :
- English
- ISSN :
- 0269-9370
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 7546413
- Full Text :
- https://doi.org/10.1097/00002030-199507000-00005