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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Abatacept
-
Adoptive Transfer
-
Animals
-
Antibodies, Blocking / administration & dosage
-
Antibodies, Monoclonal / administration & dosage
-
Antigens, CD / immunology
-
Antigens, CD / metabolism
-
Antigens, Differentiation / immunology
-
Antigens, Differentiation / metabolism
-
Autoantigens / immunology
-
Autoantigens / metabolism
-
B7-1 Antigen / immunology
-
B7-1 Antigen / metabolism
-
B7-2 Antigen
-
Boron Compounds / metabolism
-
CD28 Antigens / biosynthesis
-
CD28 Antigens / genetics
-
CD28 Antigens / immunology
-
CD28 Antigens / metabolism
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / metabolism
-
CD4-Positive T-Lymphocytes / transplantation
-
CD40 Antigens / genetics
-
CD40 Antigens / immunology
-
CD40 Antigens / metabolism
-
CD40 Ligand / genetics
-
CD40 Ligand / immunology
-
CD40 Ligand / metabolism
-
CTLA-4 Antigen
-
Epitopes, T-Lymphocyte / immunology
-
Flow Cytometry
-
Fluorescent Dyes / metabolism
-
Histocompatibility Antigens Class II / immunology
-
Histocompatibility Antigens Class II / metabolism
-
Homeostasis / genetics
-
Homeostasis / immunology*
-
Immune Sera / administration & dosage
-
Immunoconjugates*
-
Injections, Intraperitoneal
-
Kinetics
-
Lymphocyte Activation* / genetics
-
Membrane Glycoproteins / antagonists & inhibitors
-
Membrane Glycoproteins / immunology
-
Membrane Glycoproteins / 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
-
Murine Acquired Immunodeficiency Syndrome / immunology*
-
Murine Acquired Immunodeficiency Syndrome / metabolism
Substances
-
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