Advisory Committee Chair
Allan J Zajac
Advisory Committee Members
David D Chaplin
William J Britt
Judith A Kapp
Casey T Weaver
Document Type
Dissertation
Date of Award
2012
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Interactions mediated by intercellular adhesion molecule-1 (ICAM-1) enhance both the antigenic and cytokine signals that CD8 T cells perceive, and these interactions have been suggested to be required for the formation of memory CD8 T cells. Following acute lymphocytic choriomeningitis virus (LCMV) infection of ICAM-1-/- mice, we observe elevated numbers of "effector-phenotype" (CD127lo KLRG-1hi IL-2-) virus-specific CD8 T cells well into the memory phase, while the development of memory-phenotype CD8 T cells (CD127hi KLRG-1lo IL-2 producing) is not impaired. The enhanced maintenance of effector-phenotype cells is due to ICAM-1 deficiency on non-T cell subsets, suggesting a role for ICAM-1 mediated interactions with the APC in programming efficient contraction of these cells. Although memory T cells do emerge and are maintained if ICAM-1 expression is abolished, the secondary proliferative capacity of these T cells is severely curtailed. During chronic infections the development of T cell memory is corrupted as the responding cells succumb to exhaustion and possible deletion. Following chronic LCMV clone-13 infection, greater numbers of functional virus-specific CD8 T cells are observed in the tissues and secondary lymphoid organs of ICAM-1-/- mice, suggesting a role for ICAM-1 in the exhaustion of these responses. We propose a model in which ICAM-1 acts to fine tune the immune response to both low and high doses of antigen, by operating to enhance weak but restrict strong responses. In the case of infections, we propose that ICAM-1 interactions serve to further drive activation of the CD8 T cells resulting in terminal differentiation or exhaustion of the CD8 T cells and programming the downsizing of the effector response.
Recommended Citation
Cox, Maureen Ann, "Adhesion Molecule Interactions Influence the Implementation of Immune Responses to Infection" (2012). All ETDs from UAB. 1429.
https://digitalcommons.library.uab.edu/etd-collection/1429