Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals.
AIDS. 1995 Jul;9(7):695-700. Unique Identifier : AIDSLINE MED/96035231 Eriksson K; Kilander A; Hagberg L; Norkrans G; Holmgren J; Czerkinsky C; Department of Medical Microbiology and Immunology, University of; Goteborg, Sweden.
Abstract:
OBJECTIVE: To examine possible changes in mucosal B-cell activation status. 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. 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. 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. 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.
Keywords: Antibodies, Viral/*ANALYSIS Antibody Formation Antibody-Producing Cells/*IMMUNOLOGY/PATHOLOGY/VIROLOGY B-Lymphocytes/*IMMUNOLOGY/PATHOLOGY/VIROLOGY Female Gene Products, env/IMMUNOLOGY Human HIV Infections/*IMMUNOLOGY/PATHOLOGY/VIROLOGY Intestinal Mucosa/*IMMUNOLOGY/PATHOLOGY/VIROLOGY *Lymphocyte Transformation Male Protein Precursors/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
