CHARACTERISTICS OF CD4+ T-CELLS WHICH TRANSFER MURINE AIDS (MAIDS)

The murine acquired immunodeficiency syndrome (MAIDS) is caused in susceptible C57BL/6 (B6) mice by a defective murine leukemia virus (MuLV) and resembles human AIDS in several respects. The disease is characterized by hypergammaglobulinemia, polyclonal B cell activation, lymphadenopathy, and generalized immunosuppression within 5-8 weeks postinfection. The virus has been shown to infect B cells and macrophages and both T and B cells are required for MAIDS development. The manner in which T cells contribute to the disease process is not known. We report here that this retroviral infection leads to induction of a Thy-CD4(+) T cell subpopulation capable of transferring all the symptoms of MAIDS disease to normal B6 and B6 nu/nu. Essentially 100% of T cells recovered from B6 nu/nu mice, injected with CD4(+) T cells from B6 MAIDS animal, is of the Thy-CD4(+) phenotype. The proliferation of these T cells in culture and their ability to cause MAIDS in SCID mice is totally dependent on the presence of B cells. These T cells do not exhibit significant V beta restriction of their T cell receptors (TCR) and, by PCR analysis, have defective virus-specific sequences in the cellular genome. By several criteria, however, these cells do not produce the infectious virus. These results suggest that a B-cell-dependent population of CD4(+) T cells from MAIDS animals, in the absence of detectable infectious virus production, has the ability to transfer MAIDS-like disease. (C) 1994 Academic Press, Inc.