A Self-Help Program for Memory CD8+ T Cells: Positive Feedback via CD40-CD40L Signaling as a Critical Determinant of Secondary Expansion
Figure 1
Memory CD8+ T cell expansion following homologous boost is CD4+ T cell independent but CD40L dependent.
Mice primed with Lm-OVA were boosted 21 days later with the indicated dose of Lm-OVA. 5 days post-boost, OVA257–264-specific CD8+ T cells were enumerated by IFN-γ intracellular cytokine staining. (A) CD8+ splenocytes were transferred from Lm-OVA primed B6.SJL (CD45.1+) mice into C57BL/6 (CD45.2+) recipients. Recipient mice were then treated with Lm-OVA and the frequency OVA257–264-specific CD8+ T cells was determined by intracellular IFN-γ staining. (B) Mice were depleted of CD4+ cells at the time of the secondary immunization. Absolute OVA257–264-specific CD8+ T cells five days post homologous Lm-OVA prime-boost (mean±SEM, n = 5). (C-E) Mice were treated with MR1 (αCD40L) or control antibody during boost. (C) Frequency of OVA257–264-specific CD8+ T cells within total CD8+ cells with and without CD40L blockade (mean±SEM, n = 5). (D) Absolute number of IFN-γ-producing OVA257–264-specific CD8+ T cells (mean±SEM). (E) Fold expansion of OVA257–264-specific CD8+ T cells with and without CD40L blockade (mean absolute IFN-γ+ OVA257–264 -specific CD8+ T cells per group relative to mean of matched HBSS group). *, P<0.05, **P<0.01, Mann-Whitney. Data are representative of two independent experiments.