T-CELL-INDEPENDENT ANTIBODY-MEDIATED CLEARANCE OF POLYOMA-VIRUS IN T-CELL-DEFICIENT MICE

Polyomavirus (PyV) infection of SCID mice, which lack functional T and B cells, leads to a lethal acute myeloproliferative disease (AMD) and to high levels of virus replication in several organs by two wk after infection. This is in contrast to infection of T cell-deficient athym ic nude mice, which are resistant to acute PyV-induced disease and poo rly replicate the virus in their organs. This major difference in the virus load and in the outcome of PyV infection between SCID and nude m ice suggested that an efficient, T cell-independent antiviral mechanis m operates in T cell-deficient, PyV-infected mice. To investigate this possibility, mice with different genetically engineered T and/or B ce ll deficiencies and SCID mice adoptively reconstituted with B and/or T cells were infected with PyV. The results indicated that the presence of B cells in the absence of T cells protected mice from the AMD, and this was accompanied by a major reduction of PyV in all organs tested . Sera from PyV-infected T cell receptor (TCR) alpha beta knockout or TCR alpha beta gamma delta knockout mice contained IgG2a antibodies to PyV. Sera or purified immunoglobulin fractions from PyV-infected TCR alpha beta knockout mice protected SCID mice from the PyV-induced AMD. To our knowledge, this is the first report of an effective T cell-ind ependent antibody response clearing a virus and changing the outcome o f infection from 100% mortality to 100% survival.