Induction of CD4 T Cell Changes in Murine AIDS Is Dependent on Costimulation and Involves a Dysregulation of Homeostasis

Abstract

Strong CD4 T cell activation and proliferation are seen in susceptible mice infected with the murine retroviral inoculum, LP-BM5, which produces an immunodeficiency syndrome called murine AIDS (MAIDS). We developed a short term adoptive transfer model of MAIDS to examine the requirements for the CD4 T cell response. Naive CD4 T cells from uninfected donors responded quickly after adoptive transfer into MAIDS-infected hosts, becoming activated and proliferating within several days. Using blocking mAbs to costimulatory ligands and CD4 T cells deficient in expression of their receptors, we found that the CD4 T cell response requires CD28:B7.1/B7.2 interactions, but not CTLA4 or CD40-CD40 ligand interactions. Naive CD4 T cells did not respond in H-2M-deficient mice with MAIDS, suggesting that disease requires recognition of self peptide-MHC complexes. The self MHC-dependent division and accumulation of large numbers of CD4 T cells suggest that MAIDS involves a disruption of the balance of homeostatic signals. Supporting this hypothesis, CD4 T cells from mice with MAIDS failed to regulate the homeostatic division of naive CD4 T cells in a cotransfer model. Thus, a combination of up-regulation of costimulatory ligands and disruption of homeostatic control may be responsible for CD4 lymphoproliferation in MAIDS.

A role for T lymphocytes in mediating cardiac diastolic function

“…The LP-BM5 retrovirus mixture was administered intraperitoneally to mice in 0.1 ml of minimum essential medium with an esotropic titer of 4.5 log 10 plaque-forming units ϫ 10 Ϫ3 /l, which induces TH2 dominant lymphocyte function comparable with that previously published (17,20,47,58). The mice were infected with LP-BM5 2 wk before treatment with the TCR-V␤ peptides, as done previously in earlier studies (27,40,49).…”

“…We found no significant increase of LP-BM5 copy numbers as detected by cPCR over time (data not shown). LP-BM5-induced TH2 lymphocyte function is rapid and sustained until the death of the mouse (17,20,28,47,58). We have reported that ventricular dilation and decreased ␤ occurs in the absence of cardiac lymphocytic infiltrates and inflammatory mediators (4,40).…”

The Role of CD4 T Cells in the Pathogenesis of Murine AIDS

“…Several studies have examined the effects of established MAIDS disease on the CD4 T-cell compartment, i.e., characterization of CD4 T-cell anergy (2,21,41,59), but there are few prospective studies defining the role of these CD4 T-cell features in the induction of MAIDS. The molecular basis for the requirement for CD4 T cells for MAIDS induction is thus incompletely understood.…”