LOSS OF FOLLICULAR DENDRITIC CELLS IN MURINE-ACQUIRED IMMUNODEFICIENCY SYNDROME

BACKGROUND: The disease caused by HIV-1 leads to the destruction of fo llicular dendritic cells (FDC) and the follicular architecture in seco ndary lymphoid tissues. The murine acquired immuno-deficiency syndrome (MAIDS, caused by LP-BM5) serves as an animal model for study of mech anisms involved in development of retrovirus-induced immunodeficiencie s. The present study was undertaken to determine whether LP-BM5 infect ion leads to the destruction of murine FDC and the normal follicular a rchitecture in secondary lymphoid tissues. EXPERIMENTAL DESIGN: Mice w ere infected with LP-BM5, and the follicular architecture and FDC netw orks were assessed. The pathologic changes observed were correlated wi th FDC function. RESULTS: Three weeks after infection, FDC networks we re present, and they often appeared hyperplastic. However, by 1 month after infection, distorted lymphoid follicles were apparent, and the i ntensity of FDC labeling began to decline. FDC disappeared first in th e spleen, and in hyperimmunized mice, FDC in draining lymph nodes disa ppeared before FDC in nondraining lymph nodes. By 4 months, the normal follicular localization of B cells was missing, and FDC were not dete ctable in most tissues. As the FDC and the normal lymphoid architectur e degenerated, extrafollicular foci of immunoblasts and plasma cells a ppeared in areas typically reserved for T cells, and the Thy 1.2(+) T cells were dispersed. Of interest, the total number of Ig-producing ce lls increased as the disease progressed; in contrast, the number of an ti-human serum albumin-producing cells in mice immunized with human se rum albumin before infection decreased. CONCLUSIONS: These data indica te that, like HIV-1 infection, LP-BM5 infection leads to the loss of F DC and the normal follicular architecture. However, morphologic change s were not observed until after FDC had lost their normal ability to t rap and retain Ag. These data indicate that retroviral infections may cause FDC dysfunctions long before FDC are destroyed.