Tumor-Specific Responses in Lymph Nodes Draining Murine Sarcomas Are Concentrated in Cells Expressing P-Selectin Binding Sites

• Published in: The Journal of immunology (1950) 2001-09, Vol.167 (6), p.3089-3098
• Main Authors: Tanigawa, Keishi, Takeshita, Nobuhiro, Craig, Ronald A, Phillips, Katie, Knibbs, Randall N, Chang, Alfred E, Stoolman, Lloyd M
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigens, CD - analysis; Cell Differentiation; Cells, Cultured; E-Selectin - metabolism; Female; Fibrosarcoma - chemically induced; Fibrosarcoma - immunology; Fibrosarcoma - secondary; Immunization; Immunoglobulin M - metabolism; Immunomagnetic Separation; Immunophenotyping; Inflammation; Interferon-gamma - metabolism; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lymph Nodes - immunology; Lymphocyte Activation; Lymphokines - metabolism; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin - immunology; P-selectin; P-Selectin - metabolism; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Fibroblast Growth Factor - metabolism; Recombinant Fusion Proteins - metabolism; Sialoglycoproteins; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.6.3089

Tumor-draining lymph node (TDLN) cells develop substantial antitumor activity after activation on immobilized alphaCD3 and culture in low-dose IL-2. This study found that the minor subset of TDLN T cells expressing binding sites for the adhesion receptor P-selectin (Plig(high) T cells) produced T lymphoblasts with the most tumor-specific IFN-gamma synthesis in vitro and antitumor activity following adoptive transfer in vivo. The Plig(high) T cells constituted 30-fold more active than cultured TDLN cells depleted of the Plig(high) fraction before expansion (Plig(low) cells). Tumor-specific IFN-gamma synthesis in vitro paralleled the antitumor activities of the cultured fractions in vivo, implying that increased Tc1 and Th1 effector functions contributed to the tumor suppression. Neither nonspecific interaction with the P-selectin chimera used for sorting nor endogenous costimulatory activity in the Plig(high) fraction accounted for the marked increase in antitumor activities after culture. The cultured Plig(high) fraction contained a variety of potential effector cells; however, the CD8 and CD4 subsets of alphabeta T cells accounted for 95-97% of its antitumor activity. The authors propose that P-selectin sorting increased antitumor activities by concentrating Tc1 and Th1 pre-effector/effector cells before culture.