TY - JOUR
T1 - Defective Th1 and Th2 cytokine synthesis in the T-T cell presentation model for lack of CD40/CD40 ligand interaction
AU - De Vita, Lucrezia
AU - Accapezzato, Daniele
AU - Mangino, Giorgio
AU - Morrone, Stefania
AU - Santilio, Isabella
AU - Casciaro, Marco Antonio
AU - Fava, Danila
AU - Bruno, Guglielmo
AU - Del Prete, Gianfranco
AU - Santoni, Angela
AU - Barnaba, Vincenzo
PY - 1998/11
Y1 - 1998/11
N2 - In this study, T or NK cell clones used as antigen-presenting cells (T- or NK-APC) were shown to be significantly less efficient than professional APC in inducing Th1 and Th2 cytokines by antigen-specific T cell clones. This phenomenon was not related to a limited engagement of TCR by T-APC, since comparable thresholds of TCR down-regulation were shown when antigen was presented by either T-APC or professional APC. Rather, the stimulatory T-APC weakness was due to their inability, because they are CD40-, to provide the appropriate co-stimuli to responder T cells both indirectly via IL-12, and partially via direct CD40L triggering on T cells. Indeed, the simultaneous addition of IL-12 and reagents directly engaging CD40L on responder T cells restored T cell cytokine synthesis when antigen was presented by T-APC. In addition, either IL-12 production or blocking of T cell cytokine synthesis by anti-IL-12 p75 antibodies was evident only when professional APC were used in our antigen-specific system. The down-regulation of cytokine synthesis in the system of T-T cell presentation could represent a novel mechanism of immune regulation, which may intervene to switch off detrimental Th1- or Th2-mediated responses induced by antigen presentation among activated T cells infiltrating inflamed tissues.
AB - In this study, T or NK cell clones used as antigen-presenting cells (T- or NK-APC) were shown to be significantly less efficient than professional APC in inducing Th1 and Th2 cytokines by antigen-specific T cell clones. This phenomenon was not related to a limited engagement of TCR by T-APC, since comparable thresholds of TCR down-regulation were shown when antigen was presented by either T-APC or professional APC. Rather, the stimulatory T-APC weakness was due to their inability, because they are CD40-, to provide the appropriate co-stimuli to responder T cells both indirectly via IL-12, and partially via direct CD40L triggering on T cells. Indeed, the simultaneous addition of IL-12 and reagents directly engaging CD40L on responder T cells restored T cell cytokine synthesis when antigen was presented by T-APC. In addition, either IL-12 production or blocking of T cell cytokine synthesis by anti-IL-12 p75 antibodies was evident only when professional APC were used in our antigen-specific system. The down-regulation of cytokine synthesis in the system of T-T cell presentation could represent a novel mechanism of immune regulation, which may intervene to switch off detrimental Th1- or Th2-mediated responses induced by antigen presentation among activated T cells infiltrating inflamed tissues.
KW - Antigen presentation
KW - Co-stimulatory molecules
KW - Cytokine
KW - Th1
KW - Th2
UR - http://www.scopus.com/inward/record.url?scp=0031771131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031771131&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199811)28:11<3552::AID-IMMU3552>3.0.CO;2-X
DO - 10.1002/(SICI)1521-4141(199811)28:11<3552::AID-IMMU3552>3.0.CO;2-X
M3 - Article
C2 - 9842898
AN - SCOPUS:0031771131
VL - 28
SP - 3552
EP - 3563
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -