Complementary Role of CD4⁺ T Cells and Secondary Lymphoid Tissues for Cross-presentation of Tumor Antigen to CD8⁺ T Cells

Speaker: 楊育靜

Commentator: 楊倍昌 老師

Time: 13:00-14:00 10/29/2003

Place: Room 601

Abstract

MHC class I–restricted tumor antigens can be presented to CD8⁺ T cells by direct priming or indirect primeing (cross-presentation). But the contributions of these two pathways to priming tumor-specific CD8⁺ T cells and their pathophysiological relevance were vigorously debated. In this paper, the authors used 2C TCR transgenic T cells that can recognize L^d only through the direct pathway, but recognize the SIYRYYGL (SIY) peptide via both direct and indirect pathways (1, 2) to developed a tumor model. The carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled 2C T cells were adoptively transferred into B6 mice that were inoculated with either fibrosarcoma MC57G transfected with L^d (MC57-L^d) or SIY (MC57-SIY). This approach allows them to directly study early T cell priming and each step of expansion, maturation, and ultimate tumor rejection to elucidate the contributions of direct and indirect presentation pathways to CD8⁺ T cell priming and subsequent tumor rejection. Their results show that MC57-SIY, but not MC57-L^d, efficiently primes naive 2C T cells in draining lymphoid tissue leading to tumor rejection. Furthermore, they also observed the priming of 2C T cells in draining lymph nodes (DLN)-deficient mice. In the absence of DLN, CD8⁺ T cells become dependent on CD4⁺ T cells help. This paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8⁺ T cells under conditions that require either CD4⁺ T cell help, or DLN (3). Knowing how tumor antigen–specific CD8⁺ T cells are activated, by direct or indirect presentation, has an important impact on our understanding of how antigenic tumors escape recognition by CD8⁺ T cells, and may shape design of therapeutic regiments toward invigorating the cytotoxic CD8⁺ T cell response.

References

1.     Sha, W.C., et al., 1988. Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature, 336:73–76.

2.     Udaka, K., et al., 1996. Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone. J. Immunol. 157:670–678.

3.     Yu, P., et al. 2003. Complementary role of CD4⁺ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8⁺ T Cells. J. Exp. Med.197: 985-995.