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.
Authors	Michael H Yen, Nancy Lepak, Susan L Swain
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 2 Pg. 722-31 (Jul 15 2002) ISSN: 0022-1767 [Print] United States
PMID	12097374 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	4,4-difluoro-4-bora-3a,4a-diaza-s-indacene Antibodies, Blocking Antibodies, Monoclonal Antigens, CD Antigens, Differentiation Autoantigens B7-1 Antigen B7-2 Antigen Boron Compounds CD28 Antigens CD40 Antigens CTLA-4 Antigen Cd86 protein, mouse Ctla4 protein, mouse Epitopes, T-Lymphocyte Fluorescent Dyes Histocompatibility Antigens Class II Immune Sera Immunoconjugates Membrane Glycoproteins CD40 Ligand Abatacept
Topics	Abatacept Adoptive Transfer Animals Antibodies, Blocking (administration & dosage) Antibodies, Monoclonal (administration & dosage) Antigens, CD (immunology, metabolism) Antigens, Differentiation (immunology, metabolism) Autoantigens (immunology, metabolism) B7-1 Antigen (immunology, metabolism) B7-2 Antigen Boron Compounds (metabolism) CD28 Antigens (biosynthesis, genetics, immunology, metabolism) CD4-Positive T-Lymphocytes (immunology, metabolism, transplantation) CD40 Antigens (genetics, immunology, metabolism) CD40 Ligand (genetics, immunology, metabolism) CTLA-4 Antigen Epitopes, T-Lymphocyte (immunology) Flow Cytometry Fluorescent Dyes (metabolism) Histocompatibility Antigens Class II (immunology, metabolism) Homeostasis (genetics, immunology) Immune Sera (administration & dosage) Immunoconjugates Injections, Intraperitoneal Kinetics Lymphocyte Activation (genetics) Membrane Glycoproteins (antagonists & inhibitors, immunology, metabolism) Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Mice, Nude Mice, SCID Mice, Transgenic Murine Acquired Immunodeficiency Syndrome (genetics, immunology, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!