Cytotoxic T lymphocyte antigen 4 (CD152) regulates self-reactive T cells in BALB/c but not in the autoimmune NOD mouse.
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.
Piganelli
J D
JD
Barbara Davis Center for Childhood Diabetes and Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, 80262, USA.
Poulin
M
M
Martin
T
T
Allison
J P
JP
Haskins
K
K
D000069594:Abatacept; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001324:Autoantigens; D015551:Autoimmunity; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D000069594:Abatacept; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin