BONE-MARROW CONTAINS VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

Immunizing bone marrow donors prior to bone marrow transplant (BMT) ha s the potential for adoptively transferring specific immunity against opportunistic;pathogens. Studies have shown that long-term antibody pr oduction occurs in the bone marrow and that specific humoral immunity may be transferred from donor to recipient following BMT. However, the magnitude and duration of T-cell memory in the bone marrow compartmen t has not been adequately investigated. In this study, virus-specific CD8(+) T-cell responses in the bone marrow were compared with those ob served in the spleen of mice acutely infected with lymphocytic choriom eningitis virus (LCMV), During the acute stages of infection, most CD8 (+) T cells in the spleen and bone marrow showed upregulated surface e xpression of the activation/memory marker, LFA-1 (LFA-l(hi)). After cl earing LCMV infection, the antiviral immune response subsided to homeo static levels and the ratio of CD8(+)/LFA-1(hi) to CD8(+)/LFA-1(lo) T cells in the spleen and bone marrow of LCMV immune mice returned to th e value observed in naive mice. Virus-specific ex vivo effector cytoto xic T-lymphocyte (CTL) responses could be identified in both spleen an d bone marrow compartments at 8 days postinfection, LCMV-specific CTL precursor (CTLp) frequencies peaked in the bone marrow at 8 days posti nfection and averaged one in 200 to one in 650 CD8(+) T cells, a frequ ency similar to that observed in the spleen. After clearing the acute infection, potent LCMV-specific CTL memory responses could be demonstr ated in the hone marrow for at least 325 days postinfection, indicatin g long-term persistence of antiviral T cells at this site, Adoptive tr ansfer of LCMV-immune bone marrow into severe combined immunodeficienc y (SCID) mice provided protection against viral challenge, whereas SCI D mice that received naive bone marrow became chronically infected upo n challenge with LCMV, These results indicate that after acute viral i nfection, virus-specific memory T cells can be found in the hone marro w compartment and are maintained for an extended period, and when adop tively transferred into an immunodeficient host, they are capable of c onferring protection against chronic viral infection, (C) 1997 by The American Society of Hematology.