Search

The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8?? on activated CD8??+ T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells led to continued selection of mature CD8??+ memory T cells. The memory process driven by TL and CD8?? was essential for the generation of CD8??+ memory T cells in the intestine and the accumulation of highly antigen-sensitive CD8??+ memory T cells that form the first line of defense at the largest entry port for pathogens. [ABSTRACT FROM AUTHOR]

CD1d-reactive natural killer T (NKT) cells with an invariant Vα14 rearrangement (Vα14i) are a distinct subset of T lymphocytes that likely have important immune-regulatory functions. Little is known regarding the factors responsible for their peripheral survival. Using α-galactosylceramide–containing CD1d tetramers to detect Vα14i NKT cells, we show here that the expansion of Vα14i NKT cells in lymphopenic mice was not dependent on CD1d expression and was unaffected by the presence of host NKT cells. Additionally, we found that IL-15 was important in the expansion and/or survival of Vα14i NKT cells, with IL-7 playing a lesser role. These results demonstrate that the homeostatic requirements for CD1d-restricted NKT cells, which are CD4+ or CD4-CD8-, resemble those of CD8+ memory T cells. We propose that this expansion and/or survival in the periphery of Vα14i NKT cells is affected by competition for IL-15, and that IL-15–requiring cells—such as NK cells and CD8+ memory cells—may define the Vα14i NKT cell niche. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug αgalactosylceramide (αGalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4).When αGalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (>4 days) and marked by a large expansion in IFN-γ-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free αGalCer are able to induce strong IFN-γ-producing NKT responses when transferred to naïve mice, but not when transferred to αGalCer-treated recipients. In the latter, the NKT cells are anergized and can respond to glycolipid only in the presence of supplemental IL-2.Therefore, when αGalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of αGalCer on other cells. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at the Fifth International Symposium on CD1 and Natural Killer T (NKT) Cells held on March 23-27, 2009 in Kamkura Japan. Topics include the studies on innate immunity, the type 1 NKT cells or invariant NKT (iNKT) cells and the strategies to improve NKT cell immunotherapy for diseases. The symposium featured several NKT cells investigators including Masaru Taniguchi, Edward S. Morse and Louis Agassiz.

CD1d-reactive natural killer T (NKT) cells with an invariant V alpha 14 rearrangement (V alpha 14i) are a distinct subset of T lymphocytes that likely have important immune-regulatory functions. Little is known regarding the factors responsible for their peripheral survival. Using alpha-galactosylceramide-containing CD1d tetramers to detect V alpha 14i NKT cells, we show here that the expansion of V alpha 14i NKT cells in lymphopenic mice was not dependent on CD1d expression and was unaffected by the presence of host NKT cells. Additionally, we found that IL-15 was important in the expansion and/or survival of V alpha 14i NKT cells, with IL-7 playing a lesser role. These results demonstrate that the homeostatic requirements for CD1d-restricted NKT cells, which are CD4(+) or CD4(-)CD8(-), resemble those of CD8(+) memory T cells. We propose that this expansion and/or survival in the periphery of V alpha 14i NKT cells is affected by competition for IL-15, and that IL-15-requiring cells-such as NK cells and CD8(+) memory cells-may define the V alpha 14i NKT cell niche.

Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug alpha-galactosylceramide (alpha GalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When alpha GalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (>4 days) and marked by a large expansion in IFN-gamma-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free alpha GalCer are able to induce strong IFN-gamma-producing NKT responses when transferred to naïve mice, but not when transferred to alpha GalCer-treated recipients. In the latter, the NKT cells are energized and can respond to glycolipid only in the presence of supplemental IL-2. Therefore, when alpha GalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of alpha GalCer on other cells.