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, recruit ment of CD8(+) T lymphocytes may be critical for the host response that att empts to control HIV-1 replication. The present study was undertaken as no detailed assessment of lymphocyte subpopulations in HIV-1-infected lymph no des has previously been reported. Peripheral blood and single-cell suspensi ons prepared from lymph nodes of patients with HIV-1 and control subjects w ere analysed using three-colour flow cytometry. Approximately 80% of the ly mphocytes in control lymph nodes were CD3(+) T lymphocytes, of which over 6 5% were CD4(+). The majority of the CD4(+) and CD8(+) T lymphocytes obtaine d from both lymph nodes and blood of control subjects were immunologically naive (CD45RA(+)). By contrast, in HIV-1-infected patients there was a sign ificant reduction in the proportion of CD4(+) T lymphocytes and an expansio n of the CD8(+) T lymphocyte subset in both lymph nodes and peripheral bloo d. Furthermore, a high proportion of these T lymphocytes displayed a marker for immunological memory (CD45RO(+)). T lymphocytes derived from HIV-1-inf ected lymph nodes also showed altered expression of the adhesion molecules, L-selectin and very late antigen-4 (VLA-4), but not leucocyte function-ass ociated antigen-1 (LFA-1). In an in vitro adhesion assay, lymphocytes from HIV-1- infected nodes were significantly more adhesive than control lymphoc ytes on fibronectin, as well as recombinant human intercellular adhesion mo lecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) substrates . This combination of altered lymphocyte subpopulations in the HIV-1-infect ed lymph nodes, as well as enhanced adhesion phenotype and function, sugges ts that T lymphocyte traffic to lymph nodes in HIV disease may be an import ant determinant of pathogenesis.