Abstract
Cytotoxic T lymphocytes (CTL) are equipped with a range of effector functions that contribute both to the control of intracellular pathogens and dysregulated cellular proliferation and to the development of certain immunopathologies such as autoimmune disease. Qualitative analyses of various CTL responses have revealed substantial heterogeneity in the diversity of functions that are mobilized in response to antigen. Here, we studied the influence of the CD8 co-receptor, which is known to enhance antigen recognition by CTL, on the secretion of eight different cytokines and chemokines by human CTL clones using flow cytometric bead array. Our results show that abrogation of MHC class I/CD8 interactions exerts a differential influence on the distinct individual effector functions that are elicited in response to agonist ligands. The magnitude of this co-receptor blockade inhibitory effect was clearly related to the hierarchy of cytokine secretion in terms of activation threshold because those functions requiring the highest amounts of antigen were most affected. Thus, modulation of CD8 activity can effectively tune not only the sensitivity but also the qualitative profile of CTL responses.
Highlights
Cytotoxic T lymphocytes (CTL) are key components of the adaptive immune system, conferring protection against intracellular microbes and malignancies through the recognition of specific antigenic determinants expressed in association with major histocompatibility complex class I (MHCI) molecules on the cell surface
In addition to mediating the lysis of target cells by the directed release of cytotoxic agents upon activation [1], CTL are equipped with a range of effector functions that participate in the communication between different cellular components of the immune system and elicit anti-microbial activity independently of cytolytic mech
All functional outcomes resulting from antigen exposure are not affected by disruption of the MHCI/CD8 interaction
Summary
Cytotoxic T lymphocytes (CTL) are key components of the adaptive immune system, conferring protection against intracellular microbes and malignancies through the recognition of specific antigenic determinants expressed in association with major histocompatibility complex class I (MHCI) molecules on the cell surface. In addition to mediating the lysis of target cells by the directed release of cytotoxic agents upon activation [1], CTL are equipped with a range of effector functions that participate in the communication between different cellular components of the immune system and elicit anti-microbial activity independently of cytolytic mech-. Anisms [2,3,4] These involve the release of soluble molecules (cytokines and chemokines) that affect the migration and cellular functions of numerous somatic cells.
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