Advisory Committee Chair
Laurie E Harrington
Advisory Committee Members
David D Chaplin
John F Kearney
Suzanne M Michalek
Hubert M Tse
Document Type
Dissertation
Date of Award
2013
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
CD4 T cells are central to the organization of the immune response through the secretion of cytokines that recruit and activate other immune cells. Following infection and pathogen control, the majority of the effector CD4 T cells undergo apoptosis, leaving a subset that persists and gives rise to the memory T cell pool. Upon encountering the same pathogen, memory CD4 T cells respond rapidly, providing enhanced protection from re-infection. What determines which effector CD4 T cells will survive is unclear; however, there are a number of factors both intrinsic to the cell as well as external signals from the environment that can influence the fate of these cells. B cells have a number of effector capabilities that can impact CD4 T cells throughout their development and during an immune response. We show the generation of optimal CD4 T cell memory was dependent on B cells during the priming of a CD4 T cell response to Listeria monocytogenes (LM). Accordingly, the capacity of B cells to present antigen affected the formation of CD4 T cell memory. The CD4 T cell memory response was further diminished in B cell-/- mice suggesting that B cells are necessary during ontogeny as well as during the initiation of an immune response. Importantly, effector CD4 T cells are not dependent on B cells for their transition into memory cells or their maintenance; however, memory CD4 T cells are still reliant on B cells during a re-challenge for their robust expansion. The role of B cells during the recall response is not antigen presentation, further exemplifying the many aspects of B cells that can impact CD4 T cells. Although Tbet and STAT4 are essential transcription factors for Th1 differentiation, little is known about their role in CD4 T cell memory formation. In the absence of Tbet the development of central memory CD4 T cells is favored, while STAT4 does not appear to be involved in this process. Surprisingly, in the absence of Tbet and/or STAT4, these cells survive to form memory.
Recommended Citation
Mollo, Sarah B., "Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function" (2013). All ETDs from UAB. 2495.
https://digitalcommons.library.uab.edu/etd-collection/2495