The role of CD40 in peripheral T cell tolerance and immunity

TY - JOUR

T1 - The role of CD40 in peripheral T cell tolerance and immunity

AU - Diehl, L

AU - Den Boer, A T

AU - van der Voort, E I

AU - Melief, C J

AU - Offringa, R

AU - Toes, R E

PY - 2000

Y1 - 2000

N2 - CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity. The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling. Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL. Blocking of CD40-CD40L interactions can also have profound effects on the generation of T cell immunity. Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body. In most sites of the periphery interruption of CD40-CD40L interactions can lead to the induction of T cell tolerance whereas in mucosal tissues this interruption can lead to abrogation of T cell tolerance. Furthermore, in vivo CD40 activation can convert specific T cell tolerance following peptide vaccination into efficient T cell priming. Thus intervention of CD40-CD40L interactions can result in enhancement or down-modulation of T cell reactivity and therefore modulation of these interactions may form the foundation of new treatment modalities directed against malignancies, allergies, organ rejections and autoimmunity.

AB - CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity. The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling. Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL. Blocking of CD40-CD40L interactions can also have profound effects on the generation of T cell immunity. Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body. In most sites of the periphery interruption of CD40-CD40L interactions can lead to the induction of T cell tolerance whereas in mucosal tissues this interruption can lead to abrogation of T cell tolerance. Furthermore, in vivo CD40 activation can convert specific T cell tolerance following peptide vaccination into efficient T cell priming. Thus intervention of CD40-CD40L interactions can result in enhancement or down-modulation of T cell reactivity and therefore modulation of these interactions may form the foundation of new treatment modalities directed against malignancies, allergies, organ rejections and autoimmunity.

KW - Animals

KW - Antigen-Presenting Cells

KW - Antigens, CD40

KW - CD4-Positive T-Lymphocytes

KW - CD40 Ligand

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Immune System

KW - Lymphocyte Activation

KW - Models, Biological

KW - Peptides

KW - T-Lymphocytes

KW - T-Lymphocytes, Cytotoxic

KW - T-Lymphocytes, Helper-Inducer

KW - Up-Regulation

KW - Vaccines

M3 - SCORING: Journal article

C2 - 11043379

VL - 78

SP - 363

EP - 371

JO - J MOL MED

JF - J MOL MED

SN - 0946-2716

IS - 7

ER -