Requirement for CD40 Ligand, CD4 + T Cells, and B Cells in an Infectious Mononucleosis-Like Syndrome

Abstract

ABSTRACT Respiratory challenge with the murine gammaherpesvirus 68 (γHV-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 lo T cells, particularly a Vβ4 + 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 B-cell-deficient mice show no increase in Vβ4 + CD8 + T cells. Similar abrogation of the Vβ4 + CD8 + response is seen following antibody-mediated depletion of the CD4 + subset, through the numbers of CD8 + CD62L lo cells are still significantly elevated. Virus-specific CD4 + -T-cell frequencies are minimal in the CD40L −/− mice, and the Vβ4 + CD8 + population remains unexpanded. Apparently B-cell–CD4 + -T-cell interactions play a part in the γHV-68 induction of both splenomegaly and non-MHC-restricted Vβ4 + CD8 + -T-cell expansion.