Requirement for CD40 ligand, CD4+ T cells, and B cells in an infectious mononucleosis-like syndrome

Respiratory challenge with the murine gammaherpesvirus 68 (gamma HV-68) results in productive infection of the lung, the establishment of latency in B lymphocytes and other cell types, transient splenomegaly, and prolonged clonal expansion of activated CD8(+) CD62L(Io) T cells, particularly a V beta 4(+) CD8(+) population that is found in mice with different major histocompatibility complex (MHC) haplotypes. Aspects of the CD8(+)-T-cell response are substantially modified in mice that lack B cells, CD4(+) T cells, or the CD40 ligand (CD40L). The E-cell-deficient mice show no increase in V beta 4(+) CD8(+) T cells. Similar abrogation of the V beta 4(+) CD8(+) response is seen following antibody-mediated depletion of the CD4(+) subset, through the numbers of CD8(+) CD62L(Io) cells are still significantly elevated. Virus-specific CD4(+)-T-cell frequencies are minimal in the CD40L(-/-) mice, and the V beta 4(+) CD8(+) population remains unexpanded. Apparently B-cell-CD4(+)-T-cell interactions play a part in the gamma HV-68 induction of both splenomegaly and non-MHC-restricted V beta 4(+) CD8(+)-T-cell expansion.