Contribution of Thy-1−CD4+T Cells to the Disorganization of Lymphoid Follicles in Retrovirus-Induced Immunodeficiency Syndrome, MAIDS

Abstract

The destruction of the lymphoid follicle (LF) and of the follicular dendritic cell network in the secondary lymphoid organs are major pathological features in murine acquired immunodeficiency syndrome (MAIDS). These pathological changes are associated with functional deficiency of lymphocytes. However, the mechanisms involved have not been established. In MAIDS-susceptible C57BL/6 (B6) mice, the destruction of the LF occurred as early as 2–3 weeks after the infection by LP-BM5 murine leukemia virus (MuLV) and was accompanied by the intrafollicular infiltration of T cells of an unusual phenotype, Thy-1−CD4+. B6 mice, which Thy-1+T cells had been depleted by the repeated inoculation with monoclonal antibody to Thy-1 antigen, developed LF destruction after infection similar to the control B6 mice. The LP-BM5 MuLV-infected C57BL/6-nu/nu(B6-nu/nu) mice, otherwise resistant to MAIDS induction, also developed these abnormalities following the adoptive transfer of highly purified Thy-1−CD4+T cells obtained from MAIDS mice. Thus, the production of Thy-1−CD4+T cells and their infiltration into LF are thought to be involved in triggering the LF destruction. However, the cytolysis of follicular components by activated CD8+T cells or by LP-BM5 MuLV itself was a less likely mechanism as MAIDS developed in B6 mice depleted of CD8+T cell. A/J mice, which are resistant to viral infection in the presence of CD8+T cells, also developed MAIDS and LF destruction after the depletion of CD8+T cells. Furthermore, no follicular destruction was observed in infected B6-nu/numice even though they are highly sensitive to LP-BM5 MuLV.