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  • Title: Therapeutic efficacy of Th1 and Th2 L-selectin--CD4+ tumor-reactive T cells.
    Author: To WC, Seeley BM, Barthel SW, Shu S.
    Journal: Laryngoscope; 2000 Oct; 110(10 Pt 1):1648-54. PubMed ID: 11037819.
    Abstract:
    OBJECTIVE: To evaluate the cytokine secretion profile and therapeutic efficacy of Th1 CD4+ L-selectin-tumor-draining lymph node lymphocytes in the treatment of murine pulmonary metastases. STUDY DESIGN: Prospective, murine in vivo and in vitro study. METHODS: B6 mice were injected bilaterally subcutaneously with MCA 205 sarcoma cells to initiate tumor growth. Eleven days later, tumor-draining inguinal lymph nodes were harvested. Single-cell suspensions were prepared and fractionated using magnetically activated cell sorting. Sorted CD4+ L-selectin-lymphocytes were activated with anti-CD3 monoclonal antibody for 48 hours either alone to give a Th1 phenotype, or in the presence of interleukin (IL)-4 and anti-interferon-gamma (alpha-IFN-gamma) monoclonal antibody to elicit a Th2 phenotype. Activated cells were then expanded for 3 days in IL-2. Resulting cells were used to treat 3-day pulmonary metastases. Enzyme-linked immunosorbent assay and intracellular fluorescent-activated cell-sorter (FACS) scanning were used to evaluate the cytokine secretion profiles of these cells. RESULTS: Activated and expanded L-selectin- CD4+ T cells demonstrated a Th1 cytokine profile and excellent antitumor efficacy. In contrast, L-selectin- CD4+ lymphocytes activated in the presence of IL-4 and alpha-IFN-gamma monoclonal antibody demonstrated a Th2-like profile and significantly (P < .05) poorer antitumor efficacy. CONCLUSIONS: The cytokine environment during the activation of tumor-draining lymph nodes can influence the therapeutic efficacy of activated L-selectin-, CD4+ T cells. Cell mediated, Th1-dependent immunity appears to play an important role in mediating tumor regression. Culture conditions promoting Th2 cells resulted in T cells associated with diminished antitumor efficacy.
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