Therapeutic efficacy of Th1 and Th2 L-selectin--CD4+ tumor-reactive T cells.

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.

• Authors: W C To, B M Seeley, S W Barthel, S Shu
• Journal: The Laryngoscope (Laryngoscope) Vol. 110 Issue 10 Pt 1 Pg. 1648-54 (Oct 2000) ISSN: 0023-852X [Print] United States
• PMID: 11037819 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• L-Selectin
• Interleukin-10
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Cell Separation
• Female
• Immunotherapy, Adoptive (methods)
• In Vitro Techniques
• Interferon-gamma (analysis)
• Interleukin-10 (analysis)
• Interleukin-4 (analysis)
• L-Selectin (immunology)
• Lung Neoplasms (secondary, therapy)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Prospective Studies
• Sarcoma, Experimental (therapy)
• Th1 Cells (immunology)
• Th2 Cells (immunology)