| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Research Abstract |
Memory CD8 T cells are long-lived antigen (Ag)-specific CD8 T cells which respond quickly, proliferate robustly, and exert effector functions faster than naive CD8 T cells upon reencounter with the specific Ags. Memory CD8 T cells are maintained at a stable size over a long period of time, but the mechanisms by which their population size is maintained remain elusive. It has been proposed that the maintenance of memory CD8 T cells depends on “CD4 T cell help”, based on the observation that CD8+ T cells which have been primed with Ags in wild-type (WT) mice survive poorly when transferred into MHCII-/- hosts as comparedto WT hosts. Our results clearly show that the impaired maintenance of memory CD8 T cells in MHCII-/- mice is not due to the absence of CD4+ helper T cells. This was shown by transferring Ag-primed CD8+ T cells into WT mice treated with the anti-CD4 GK1.5 mAb, or CD4-/- mice, or ThPOK mutant mice, all of which lack functional CD4+ helper T cells. We also found that MHCII molecules expressed by hematopoietic cells, not by non-hematopoietic cells, are required for memory CD8 T cell maintenance. The mRNA expression levels of IL-7 and IL-15, cytokines reported tobe important for memory CD8 T cell homeostasis, were comparable in the spleens of MHCII-/- and WT mice. We have not found the different expression levels of cytokines, chemokines, and growth factors in the serum of MHCII-/- and WT mice so far. However, microarray analysis of genes expressed by transferred CD8 T cells in MHCII-/- and WT mice displayed 77 different expression levels of genes. We are currently attemptingto uncover the function of these candidate genes in memory CD8 T cell maintenance.
|
