NOD.Cd1-/- mice have increased numbers of CD4+CD25+Foxp3+ T regulatory cells in the periphery

Recent studies indicate Natural Killer T (NKT) lymphocytes and Regulatory T (Treg) cells interact to regulate immune responses. NOD mice bearing a targeted deletion of the NKT cell restriction molecule, CD1d, lack NKT cells. To determine whether absence of NKT cells has an effect on Treg numbers, NOD/Lt and NOD.Cd1-/- mice were examined for differences in their Treg population. Flow cytometric analysis of 10-week old female mice of both strains revealed that NOD.Cd1-/- mice have a higher number of CD4+CD25+Foxp3+ T cells in both the spleen and liver. Further studies on differences in regulatory T cells between these strains at different ages and the effect of adoptive transfer of NKT cells on Treg cells would give us a better understanding about interactions of these two populations

An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I− variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I− RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3− NK1.1+ cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I− prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte–mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I− tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum

Ferromagnetic phase transition for the spanning-forest model (q \to 0 limit of the Potts model) in three or more dimensions

We present Monte Carlo simulations of the spanning-forest model (q \to 0 limit of the ferromagnetic Potts model) in spatial dimensions d=3,4,5. We show that, in contrast to the two-dimensional case, the model has a "ferromagnetic" second-order phase transition at a finite positive value w_c. We present numerical estimates of w_c and of the thermal and magnetic critical exponents. We conjecture that the upper critical dimension is 6.Comment: LaTex2e, 4 pages; includes 6 Postscript figures; Version 2 has expanded title as published in PR

Critical speeding-up in a local dynamics for the random-cluster model

We study the dynamic critical behavior of the local bond-update (Sweeny) dynamics for the Fortuin-Kasteleyn random-cluster model in dimensions d=2,3, by Monte Carlo simulation. We show that, for a suitable range of q values, the global observable S_2 exhibits "critical speeding-up": it decorrelates well on time scales much less than one sweep, so that the integrated autocorrelation time tends to zero as the critical point is approached. We also show that the dynamic critical exponent z_{exp} is very close (possibly equal) to the rigorous lower bound \alpha/\nu, and quite possibly smaller than the corresponding exponent for the Chayes-Machta-Swendsen-Wang cluster dynamics.Comment: LaTex2e/revtex4, 4 pages, includes 5 figure

Dynamic critical behavior of the Chayes-Machta-Swendsen-Wang algorithm

We study the dynamic critical behavior of the Chayes-Machta dynamics for the Fortuin-Kasteleyn random-cluster model, which generalizes the Swendsen-Wang dynamics for the q-state Potts model to noninteger q, in two and three spatial dimensions, by Monte Carlo simulation. We show that the Li-Sokal bound z \ge \alpha/\nu is close to but probably not sharp in d=2, and is far from sharp in d=3, for all q. The conjecture z \ge \beta/\nu is false (for some values of q) in both d=2 and d=3.Comment: Revtex4, 4 pages including 4 figure

CD1d-restricted NKT cells: an interstrain comparison

CD1d-restricted Va14-Ja281 invariant abTCR1 (NKT) cells are well defined in the C57BL/6 mouse strain, but they remain poorly characterized in non-NK1.1-expressing strains. Surrogate markers for NKT cells such as abTCR1CD42CD82 and DX51CD31 have been used in many studies, although their effectiveness in defining this lineage remains to be verified. Here, we compare NKT cells among C57BL/6, NK1.1-congenic BALB/c, and NK1.1-congenic nonobese diabetic mice. NKT cells were identified and compared using a range of approaches: NK1.1 expression, surrogate phenotypes used in previous studies, labeling with CD1d/a-galactosylceramide tetramers, and cytokine production. Our results demonstrate that NKT cells and their CD4/CD8-defined subsets are present in all three strains, and confirm that nonobese diabetic mice have a numerical and functional deficiency in these cells. We also highlight the hazards of using surrogate phenotypes, none of which accurately identify NKT cells,and one in particular (DX51CD31) actually excludes these cells. Finally, our results support the concept that NK1.1 expression may not be an ideal marker for CD1d-restricted NKT cells, many of which are NK1.1-negative, especially within the CD41 subset and particularly in NK1.1-congenic BALB/c mice

Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells

iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development and separates, the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment

Some geometric critical exponents for percolation and the random-cluster model

We introduce several infinite families of new critical exponents for the random-cluster model and present scaling arguments relating them to the k-arm exponents. We then present Monte Carlo simulations confirming these predictions. These new exponents provide a convenient way to determine k-arm exponents from Monte Carlo simulations. An understanding of these exponents also leads to a radically improved implementation of the Sweeny Monte Carlo algorithm. In addition, our Monte Carlo data allow us to conjecture an exact expression for the shortest-path fractal dimension d_min in two dimensions: d_min = (g+2)(g+18)/(32g) where g is the Coulomb-gas coupling, related to the cluster fugacity q via q = 2 + 2 cos(g\pi/2) with 2 \le g \le 4.Comment: LaTeX2e/Revtex4. Version 2 is completely rewritten to make the exposition more reader-friendly; it consists of a 4-page main paper (including 3 figures) and a 2-page EPAPS appendix (given as a single Postscript file). To appear in Phys Rev