A CRITICAL ROLE FOR NEUTRALIZING-ANTIBODY-PRODUCING B-CELLS CD4(-CELLS, AND INTERFERONS IN PERSISTENT AND ACUTE INFECTIONS OF MICE WITH LYMPHOCYTE CHORIOMENINGITIS VIRUS - IMPLICATIONS FOR ADOPTIVE IMMUNOTHERAPY OF VIRUS CARRIERS() T)

This study demonstrates that neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons (IFNs) are of key importance in virus control both in adoptive immunotherapy of persistent infection and in the late phase of acute infection with the WE strain of lymphocytic ch oriomeningitis virus (LCMV), We report the following results, (i) Clea rance of LCMV-WE from C57BL/6 carrier mice by adoptive transfer of mem ory spleen cells requires B cells and CD4(+) T cells but not necessari ly CD8(+) T cells, (ii) At the doses examined, CD8(+). T cells contrib ute to the initial reduction of viral titers but ale alone not suffici ent to clear the virus because they are exhausted, (iii) In the presen ce of functional IFN-gamma, virus clearance correlates well with the g eneration of neutralizing antibodies in the treated carrier mice, (iv) In the absence of receptors for IFN-gamma, virus clearance is not ach ieved. (v) Adoptive immunotherapy of mice persistently infected with a distinct virus isolate, LCMV-Armstrong, revealed only low levels of n eutralizing antibodies; in this case, CD8(+) T cells were needed for v irus clearance in addition to B and CD4(+) T cells. (vi) After low dos e infection of C57BL/6 mice with LCMV-WE, virus is eliminated below de tectable levels by CD8(+) T tells, but long-term (>2 months) virus con trol is usually not achieved in the absence of B cells or CD4(+) T cel ls; reappearance of the virus is paralleled tither by exhaustion of vi rus-specific cytotoxic T lymphocytes or lethal immunopathology, These findings are of importance for adoptive immunotherapy strategies again st persistent virus Infections in humans.