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Murine AIDS requires CD154/CD40L expression by the CD4 T cells that mediate retrovirus-induced disease: Is CD4 T cell receptor ligation needed?

Abstract
LP-BM5, a retroviral isolate, induces a disease featuring an acquired immunodeficiency syndrome termed murine AIDS (MAIDS). Many of the features of the LP-BM5-initiated disease are shared with HIV/AIDS. Our lab has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD40 on B cells by CD154 on CD4 T cells. Despite this strict requirement for CD154 expression, whether CD4 T cell receptor (TCR) occupancy is essential for the induction of MAIDS is unknown. To block TCR engagement, Tg mouse strains with monoclonal TCR of irrelevant peptide/MHC specificities, all on MAIDS-susceptible genetic backgrounds, were tested: the study of a panel of TCR Tg CD4 T cells controlled for the possibility of serendipitous crossreactive recognition of virus-associated or induced-self peptide, or superantigen, MHC complexes by a given TCR. The results argue that TCR engagement is not necessary for the induction of MAIDS.
AuthorsWen Li, William R Green
JournalVirology (Virology) Vol. 360 Issue 1 Pg. 58-71 (Mar 30 2007) ISSN: 0042-6822 [Print] United States
PMID17113120 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, HIV
  • RAG-1 protein
  • CD40 Ligand
Topics
  • Animals
  • CD4-Positive T-Lymphocytes (metabolism)
  • CD40 Ligand (metabolism)
  • Gene Deletion
  • Homeodomain Proteins (genetics)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Murine Acquired Immunodeficiency Syndrome (immunology)
  • Receptors, Antigen, T-Cell, alpha-beta (deficiency, genetics)
  • Receptors, HIV
  • Retroviridae (pathogenicity)
  • Virulence (immunology)

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