Kupfer-type immunological synapse characteristics do not predict anti-brain tumor cytolytic T-cell function in vivo

YANG; SANDERSON; WAWROSKY; PUNTEL; CASTRO; LOWENSTEIN

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2010 p. 4716 - 4721

0027-8424

To analyze the in vivo structure of antigen-specific immunologicalsynapses during an effective immune response, we establishedbrain tumors expressing the surrogate tumor antigen ovalbuminand labeled antigen-specific anti-glioma T cells using specifictetramers. Using these techniques,wedetermined that a significantnumber of antigen-specific T cells were localized to the brain tumorand surrounding brain tissue and a large percentage could beinduced to express IFNγ when exposed to the specific ovalbuminderivedpeptide epitope SIINFEKL. Detailed morphological analysisof T cells immunoreactive for tetramers in direct physical contactwith tumor cells expressing ovalbumin indicated that the interfacebetween T cells and target tumor cells displayed various morphologies,including Kupfer-type immunological synapses. Quantitativeanalysis of adjacent confocal optical sections was performed todetermine if the higher frequency of antigen-specific antiglioma Tcells present in animals that developed an effective antitumorimmune response could be correlated with a specific immunologicalsynapticmorphology. Detailed in vivo quantitative analysis failed todetect an increased proportion of immunological synapses displayingthe characteristic Kupfer-type morphology in animals mountinga strong and effective antitumor immune response as comparedwith those experiencing a clinically ineffective response. We concludethat an effective cytolytic immune response is not dependenton an increased frequency of Kupfer-type immunological synapsesbetween T cells and tumor cells