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Tumor-specific responses in lymph nodes draining murine sarcomas are concentrated in cells expressing P-selectin binding sites

Authors :
Ronald A. Craig
Nobuhiro Takeshita
Lloyd M. Stoolman
Keishi Tanigawa
Katie Phillips
Alfred E. Chang
Randall N. Knibbs
Source :
Journal of immunology (Baltimore, Md. : 1950). 167(6)
Publication Year :
2001

Abstract

Tumor-draining lymph node (TDLN) cells develop substantial antitumor activity after activation on immobilized αCD3 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 (Plighigh T cells) produced T lymphoblasts with the most tumor-specific IFN-γ synthesis in vitro and antitumor activity following adoptive transfer in vivo. The Plighigh T cells constituted 30-fold more active than cultured TDLN cells depleted of the Plighigh fraction before expansion (Pliglow cells). Tumor-specific IFN-γ 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 Plighigh fraction accounted for the marked increase in antitumor activities after culture. The cultured Plighigh fraction contained a variety of potential effector cells; however, the CD8 and CD4 subsets of αβ 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.

Details

ISSN :
00221767
Volume :
167
Issue :
6
Database :
OpenAIRE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Accession number :
edsair.doi.dedup.....27bfacdde2ccf126e48d310a9976f239