Acquired immunological tolerance in aged mice III. The contribution of lymphoid cells and their environments to the age related resistance to tolerance induction

Abstract Whether lymphoid cells or their environment are responsible for the decreased tolerogen sensitivity of aged mice was examined using an adoptive transfer system. Bone marrow cells form old (24 months), middle aged (12 months) and young adult mice (2 months) were equally sensitive to tolerance induction with deaggregated human immunoglobulin (DHGG) when they were transplanted into young lethally irradiated syngeneic hosts. Adoptively transferred splenocytes also showed no age related difference in tolerogen sensitivity. Thus, the age related difference seen in the intact animal is due largely to environmental factors acting on lymphoid cells in the aged animal. The role of lipopolysaccharide (LPS) as one such environmental factor affecting tolerance induction was investigated. LPS administered to aged mice produced greater polyclonal B cell activation and autoantibody formation than it did in young animals. When LPS was administered shortly after HDGG injection it converted the tolerogen to an immunogen with greater efficiency in aged animals.