Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals.
OBJECTIVE
To examine possible changes in mucosal B-cell activation status.


METHODS
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.
Eriksson
K
K
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Kilander
A
A
Hagberg
L
L
Norkrans
G
G
Holmgren
J
J
Czerkinsky
C
C
D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D011498:Protein Precursors / Q000276:immunology
D000914:Antibodies, Viral; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors