Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule.
In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease.
Linsley
P S
PS
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Wallace
P M
PM
Johnson
J
J
Gibson
M G
MG
Greene
J L
JL
Ledbetter
J A
JA
Singh
C
C
Tepper
M A
MA
D000069594:Abatacept; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D060908:CTLA-4 Antigen; D006224:Cricetinae; D004912:Erythrocytes / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000069594:Abatacept; D006433:Hemocyanins