CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues. Academic Article uri icon

Overview

abstract

  • We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and in vivo in which the concentration of antigen-specific CD8+ T cells determines the efficiency with which these cells kill cognate antigen-expressing melanoma cells in packed cell pellets, in three-dimensional collagen-fibrin gels in vitro, and in established melanomas in vivo. In combination with a clonogenic assay for melanoma cells, collagen-fibrin gels are 4,500-5,500-fold more sensitive than the packed cell pellet-type assays generally used to measure CD8+ T cell cytolytic activity. An equation previously used to describe neutrophil bactericidal activity in vitro and in vivo also describes antigen-specific CD8+ T cell-mediated cytolysis of cognate antigen-expressing melanoma cells in collagen-fibrin gels in vitro and in transplanted tumors in vivo. We have used this equation to calculate the critical concentration of antigen-specific CD8+ T cells, which is the concentration of these cells required to hold constant the concentration of a growing population of cognate antigen-expressing melanoma cells. It is approximately 3.5x10(5)/ml collagen-fibrin gel in vitro and approximately 3x10(6)/ml or /g melanoma for previously published studies of ex vivo-activated adoptively transferred tumor antigen-specific CD8+ T cell killing of cognate antigen-expressing melanoma cells in established tumors in vivo. The antigen-specific CD8+ T cell concentration required to kill 100% of 2x10(7)/ml cognate antigen-expressing melanoma cells in collagen fibrin gels is >or=10(7)/ml of gel.

authors

  • Budhu, Sadna
  • Loike, John D
  • Pandolfi, Ashley
  • Han, Soo
  • Catalano, Geoffrey
  • Constantinescu, Andrei
  • Clynes, Raphael
  • Silverstein, Samuel C

publication date

  • January 11, 2010

Research

keywords

  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes
  • Melanoma

Identity

PubMed Central ID

  • PMC2812553

Scopus Document Identifier

  • 76149114584

Digital Object Identifier (DOI)

  • 10.1016/0022-1759(86)90079-7

PubMed ID

  • 20065066

Additional Document Info

volume

  • 207

issue

  • 1