TY - JOUR
T1 - Cytotoxic T lymphocyte antigen 4 (CD152)regulates self-reactive T cells in BALB/c but not in the autoimmune nod mouse
AU - Piganelli, Jon D.
AU - Poulin, Michelle
AU - Martin, Tracy
AU - Allison, James P.
AU - Haskins, Kathryn
N1 - Funding Information:
This work was supported by a postdoctoral fellowship No. 396142 from the Juvenile Diabetes Foundation to J.P. and by NIH RO1 DK50561 to K.H.
PY - 2000
Y1 - 2000
N2 - Recent studies demonstrated that engagement of cytotoxic T lymphocyte antigen 4 (CTLA-4)/(CD152) generates an inhibitory signal to T cells which arrests an on-going immune response. Since aberrant CD152 activity is thought to contribute to autoimmunity, we examined the effect of CD152-mediated inhibitory signals on the response to self and foreign antigens in autoimmune, diabetes-prone NOD and non-autoimmune BALB/c mice. The interaction of CD152 with its ligand B7 was prevented by treating the mice with anti-CD152 blocking antibody, before and following immunization of the mice with the self-antigen, syngeneic islet cells, or the foreign antigen, key-hole limpet hemocyanin (KLH). CD152 blockade in BALB/c mice stimulated a robust islet-specific T cell-mediated immune response compared to control antibody-treated mice. The augmentation of T cell responses in BALB/c mice was consistent with the role proposed for CD152 as a down-regulator of T cell activation responses. Furthermore, CD152 blockade unmasked islet cell specific autoreactive T cells in the non-autoimmune BALB/c mouse. Conversely, CD152 blockade in NOD mice failed to regulate islet-specific auto-reactive T cell responses. However, CD152 blockade enhanced the T cell response to the exogenous, foreign antigen KLH in both non-autoimmune BALB/c and autoimmune NOD mice. Collectively, these results suggest that there is not a global defect in CD152-mediated regulation of peripheral T cell immune responses in NOD autoimmune mice but rather, a defect specific to T cells recognizing self antigen. (C) 2000 Academic Press.
AB - Recent studies demonstrated that engagement of cytotoxic T lymphocyte antigen 4 (CTLA-4)/(CD152) generates an inhibitory signal to T cells which arrests an on-going immune response. Since aberrant CD152 activity is thought to contribute to autoimmunity, we examined the effect of CD152-mediated inhibitory signals on the response to self and foreign antigens in autoimmune, diabetes-prone NOD and non-autoimmune BALB/c mice. The interaction of CD152 with its ligand B7 was prevented by treating the mice with anti-CD152 blocking antibody, before and following immunization of the mice with the self-antigen, syngeneic islet cells, or the foreign antigen, key-hole limpet hemocyanin (KLH). CD152 blockade in BALB/c mice stimulated a robust islet-specific T cell-mediated immune response compared to control antibody-treated mice. The augmentation of T cell responses in BALB/c mice was consistent with the role proposed for CD152 as a down-regulator of T cell activation responses. Furthermore, CD152 blockade unmasked islet cell specific autoreactive T cells in the non-autoimmune BALB/c mouse. Conversely, CD152 blockade in NOD mice failed to regulate islet-specific auto-reactive T cell responses. However, CD152 blockade enhanced the T cell response to the exogenous, foreign antigen KLH in both non-autoimmune BALB/c and autoimmune NOD mice. Collectively, these results suggest that there is not a global defect in CD152-mediated regulation of peripheral T cell immune responses in NOD autoimmune mice but rather, a defect specific to T cells recognizing self antigen. (C) 2000 Academic Press.
KW - Autoimmunity CD152
KW - Co-stimulatory molecules
KW - Diabetes
KW - NOD
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U2 - 10.1006/jaut.1999.0353
DO - 10.1006/jaut.1999.0353
M3 - Article
C2 - 10677243
AN - SCOPUS:0033847990
SN - 0896-8411
VL - 14
SP - 123
EP - 131
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 2
ER -