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. Author manuscript; available in PMC: 2015 May 5.
Published in final edited form as: Sci Transl Med. 2014 Nov 5;6(261):261ra151. doi: 10.1126/scitranslmed.3010162

Fig. 6. CD4+ M28z T cells augment CD8+ accumulation that is enhanced with preactivation.

Fig. 6

(A–C) Unsorted M28z and Mz or bead-sorted CD4+ and CD8+ T cells were assayed. M28z CD4+ T cells show (A) higher cytokine secretion (from 4- to 14-fold; ***P<0.001 by Student's t test) and (B) profound T-cell expansion without exogenous IL-2. (C) CD4+ M28z activation facilitates robust CD8+ M28z T-cell accumulation upon repeated antigen stimulation in vitro. (D) Antigen-activated CD4+ M28z activation facilitates robust CD8+ M28z T-cell accumulation in vivo. Isolated CD8+ effLuc M28z T cells were intrapleurally administered to MSLN+ pleural tumor–bearing mice with either CD4+ M28z (n=6) or CD4+ control–transduced T cells (n=6) and were serially imaged. One representative mouse (n=6 per group; left) displays increased CD8+ M28z T-cell accumulation in the presence of CD4+ M28z. (E) The average accumulation of CD8+ CAR+ T cells was calculated at the indicated intervals (P values as shown calculating fold increase from 16 to 72 hours, n=6 per group). (F) Preactivation of M28z CD4+ enhances CD8+ proliferation, compared with simultaneous activation of CD4+. Bead-sorted CD8+ Mz or M28z T cells were cocultured with either corresponding Mz or M28z CD4+ or preactivated CD4+ T cells (activated on MSLN+ tumor cells 24 h before the assay). Preactivation of M28z CD4+ enhances the accumulation of CD8+ to a greater degree than does CD8+ and CD4+ concurrent stimulation.