| Autor: |
Hughes, D. P. M., Baskar, D., Urban, F. A., Friedman, M. S., Braun, T. M., MeDonagh, K. T. |
| Předmět: |
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| Zdroj: |
Cytotherapy (Taylor & Francis Ltd); Oct2005, Vol. 7 Issue 5, p1-1, 1p |
| Abstrakt: |
Background Adoptive immunotherapy with T cells activated through CD3 alone requires exogenous IL-2 for T-cell function and survival after transfer, but the in vivo cytokine requirement of T cells activated through CD3 and CD28 is unknown. We hypothesized that CD3/ CD28-activated T cells, unlike those activated through CD3 alone, might develop into long-lived memory T cells, either with or without systemic IL-2. Methods We used MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, specific for the surrogate tumor Ag ovalbumin (OVA), to assess the trafficking kinetics, antigenic responsiveness and anti-tumor efficacy of dual-activated T cells in vivo as a function of IL-2 administration. At days 7, 14, and 28 after transfer lymph node cells and splenocytes were examined for donor cell persistence and antigenic responsiveness by FAGS and ELISA, respectively. Results In IL -2-treated mice, donor CD8 + T cells persisted and developed a memory phenotype, based on CD44 and Ly6c expression at day 28, while mice given no IL-2 bad fewer donor cells at all time points. OVA-specific release of IFN-γ was higher from lymphocytes of IL-2- treated mice compared with no-IL -2 mice (P < 0.02 at all time points). In mice challenged with an OVA-bearing subline of the AML leukemia model C1498, IL-2 did not confer added protection from tumor challenge at 1 or 2 weeks after adoptive transfer but gave improved survival at 4 weeks post-transfer. Discussion We conclude that exogenous IL-2 is not required for anti-tumor activity of CD3/CD28-activated CD8+ cells early after adoptive transfer, but promotes T-cell persistence that confers disease protection at more remote times. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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