CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes

By E. Janssen, E. Lemmens, T. Wolfe, U. Christen, M. Herrath, S. Schoenberger. Nature, 2003

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Therapeutic cancer vaccines. (2010, background): “CD4+ T cells are needed for optimal and sustained effector CD8+ T cell responses (120–124) as well as induction and maintenance of CD8+ memory (125, 126).”
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2 (2012, background): “Furthermore, it was recently elucidated that PD-1 is expressed on several unique T cell subsets, exhausted T cells (Janssen et al., 2003; Barber et al., 2006; Day et al., 2006), regulatory T (T reg) cells (Nishimura et al., 1996), and senescent T cells (Shimatani et al., 2009).”
CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells (2005, background): “Because absence of T cell help can hinder the in vivo maintenance of CD8 T cells and development of memory T cells (4, 6, 7, 30), we surmised that effector CD8 T cells also needed help to induce the regression of established tumors, in addition to removal of Treg cells.”