TY - JOUR
T1 - CTLA-4
T2 - A negative regulator of autoimmune disease
AU - Karandikar, Nitin J.
AU - Vanderlugt, Carol L.
AU - Walunas, Theresa L.
AU - Miller, Stephen D.
AU - Bluestone, Jeffrey A.
PY - 1996/8/1
Y1 - 1996/8/1
N2 - CTLA-4, a CD28 homologue expressed on activated cells, binds with high affinity to the CD28 ligand, B and-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-161-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vitro administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA- 4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.
AB - CTLA-4, a CD28 homologue expressed on activated cells, binds with high affinity to the CD28 ligand, B and-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-161-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vitro administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA- 4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.
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U2 - 10.1084/jem.184.2.783
DO - 10.1084/jem.184.2.783
M3 - Article
C2 - 8760834
AN - SCOPUS:0029789389
SN - 0022-1007
VL - 184
SP - 783
EP - 788
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -