CD4 T-CELL ANERGY IN MURINE AIDS - COSTIMULATION VIA CD28 AND THE ADDITION OF IL-12 ARE NOT SUFFICIENT TO RESCUE ANERGIC CD4 T-CELLS

Murine acquired immunodeficiency syndrome (MAIDS) is a fatal disease i nduced by a mixture of retroviruses known as BM5. It is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, loss of T an d B cell function, and development of B cell lymphomas. As the disease progresses, by wk 8 of infection, CD4 T cell response to Ags and mito gens is severely curtailed and the CD4 T cell population becomes anerg ic. We examined responses of anergic CD4 T cells upon addition of a co stimulatory signal (anti-CD28) and a cytokine (IL-12), which might hel p to restore the function of cells, We report that proliferation and c ytokine production were restored in the early stages of infection by t he strategies we tested, but not at later stages when anergy was well established. We also examined the effect of the same treatments on ane rgy of CD4 T cells from thymectomized, BM5-infected mice to determine whether the rescue seen was due to cells freshly derived from the thym us. We report that proliferation and cytokine production decreased in thymectomized mice even at wk 4 of infection, indicating that cells th at are freshly derived from thymus are the ones responding to treatmen t. This study indicates that once anergy has been established in MAIDS , it cannot be reversed by providing costimulation via CD28 and IL-12, Anergy of CD4 T cells in MAIDS appears to be different from that seen in other systems, both in underlying cause and in the ability of the cells to revert to a normal state.