Document 0911
 DOCN  M9540911
 TI    In vitro cytolytic activity of lymphocytes from tumor-draining lymph
       nodes is associated with increased numbers of CD8+ cells and increased
       cytokine production.
 DT    9504
 AU    Holley D; Freeman J; Hamby L; Mattingly C; McGrath PC; University of
       Kentucky, Department of Surgery, Lexington; 40536-0084.
 SO    J Surg Res. 1995 Jan;58(1):33-7. Unique Identifier : AIDSLINE
       MED/95131548
 AB    A murine footpad tumor model was used to determine the cytotoxic
       activity, tumor specificity, phenotypic profile, and cytokine production
       of stimulated cells from draining lymph nodes (DLN). Popliteal DLN from
       5-day-old P-815 footpad tumors were stimulated with 10(-7) M phorbol 12,
       13-dibutyrate +5 x 10(-7) M ionomycin for 16 hr and cultured in IL-2 (20
       units/ml) for 7 or 14 days without autologous tumor. Most cells in both
       groups were CD3+ (93% at Day 7, 99% at Day 14); however, the percentage
       of CD8+ cells increased as the cell population matured in the presence
       of low-dose IL-2. On Day 7, the phenotypic profile was 62% CD4+ and 29%
       CD8+, whereas on Day 14 it was 16% CD4+ and 81% CD8+. Similarly, in
       vitro cytokine production increased with time in culture. After 7 days,
       the level of tumor necrosis factor-alpha (TNF-alpha) was 220 pg/mL and
       the interferon-gamma (IF-gamma) production was 150 pg/ml. At Day 14 the
       TNF level had increased to 500 pg/ml, and IF production had increased to
       350 pg/ml. These increases in the CD8+ population and in cytokine
       production correlated with the increase in the percentage of target
       cells killed by the DLN cells. Cytolytic activity against P-815 was only
       13% on Day 7 but 39% on Day 14. Neither group of effector cells (Day 7
       or Day 14) had any cytolytic activity against the syngeneic tumor cell
       line L-1210, demonstrating the tumor specificity of the DLN cells. We
       describe a model for generating tumor-specific cytotoxic T-cells that
       have significant cytokine production, which may account for previously
       described in vivo activity.
 DE    Animal  Cytokines/*BIOSYNTHESIS  CD4-CD8 Ratio  CD8-Positive
       T-Lymphocytes/*PATHOLOGY  Female  Foot  Lymph
       Nodes/*METABOLISM/*PATHOLOGY  Mice  Mice, Inbred DBA  Neoplasms,
       Experimental/*METABOLISM/*PATHOLOGY  Phenotype  T-Lymphocytes,
       Cytotoxic/*PHYSIOLOGY  Time Factors  JOURNAL ARTICLE

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