Immunologic Memory Cells of Bone Marrow Origin

Abstract

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F1 mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process.

Clinical Applications of Adoptive Natural Killer Cell Immunotherapy for Cancer: Current Status and Future Prospects

“…Inanallogeneicsetting,NKcellsexhibitalloreactionsthrough KIRsasinhibitoryreceptorsforselfHLAclassI [33].Murine transplant models illustrated the potential beneficial role of NK cells in haploidentical stem cell transplant [34][35][36] prob ablythroughthefollowingtheoreticalmechanisms:i)targeting host T lymphocytes that may improve engraftment of the MHCmismatched bone marrow; ii) targeting host dendritic cellsresultingindecreasedantigenpresentationbyhostden driticcellsandhencepreventingTcellmediatedGVHD;iii) targeting leukemic cells which may initiate a graftversus leukemia(GVL)effectanddecreaserelapse;andiv)improv ingimmunereconstitutionwhichmaydecreasetheriskofop portunisticinfections [37,38]. The role of NK cell alloreactivity in a KIRmismatched settingwasfirstdescribedbytheRuggerigroupin2002 [36].…”