Phenotypic and functional characterization of lymphocytes derived from normal and HIV-1-infected human lymph nodes.
Lymph nodes are the major site of cell-to-cell transmission and replication of HIV-1. Trafficking of CD4+ T lymphocytes into lymph nodes provides a continual supply of susceptible target lymphocytes, and conversely, recruitment of CD8+ T lymphocytes may be critical for the host response that attempts to control HIV-1 replication. The present study was undertaken as no detailed assessment of lymphocyte subpopulations in HIV-1-infected lymph nodes has previously been reported. Peripheral blood and single-cell suspensions prepared from lymph nodes of patients with HIV-1 and control subjects were analysed using three-colour flow cytometry. Approximately 80% of the lymphocytes in control lymph nodes were CD3+ T lymphocytes, of which over 65% were CD4+. The majority of the CD4+ and CD8+ T lymphocytes obtained from both lymph nodes and blood of control subjects were immunologically naive (CD45RA+). By contrast, in HIV-1-infected patients there was a significant reduction in the proportion of CD4+ T lymphocytes and an expansion of the CD8+ T lymphocyte subset in both lymph nodes and peripheral blood. Furthermore, a high proportion of these T lymphocytes displayed a marker for immunological memory (CD45RO+). T lymphocytes derived from HIV-1-infected lymph nodes also showed altered expression of the adhesion molecules, L-selectin and very late antigen-4 (VLA-4), but not leucocyte function-associated antigen-1 (LFA-1). In an in vitro adhesion assay, lymphocytes from HIV-1-infected nodes were significantly more adhesive than control lymphocytes on fibronectin, as well as recombinant human intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) substrates. This combination of altered lymphocyte subpopulations in the HIV-1-infected lymph nodes, as well as enhanced adhesion phenotype and function, suggests that T lymphocyte traffic to lymph nodes in HIV disease may be an important determinant of pathogenesis.
Tedla
N
N
Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Dwyer
J
J
Truskett
P
P
Taub
D
D
Wakefield
D
D
Lloyd
A
A
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D015815:Cell Adhesion Molecules