THE ALLOGENEIC EFFECT IN INBRED MICE : IV. REGULATORY INFLUENCES OF GRAFT-VS.-HOST REACTIONS ON HOST T LYMPHOCYTE FUNCTIONS

The studies presented herein were designed to directly evaluate the effects of a transient GVH reaction on T lymphocyte functions. To this end, we have shown that generation of carrier-specific helper cell function can be significantly influenced by the allogeneic effect. Thus, carrier-primed helper cells derived from CAF1 donor mice were generally much more active in specifically cooperating with syngeneic 2,4-dinitrophenyl (DNP)-primed B cells in adoptive recipients when parental A strain lymphocytes had been administered at some time during the priming regimen. This was true when allogeneic cells were administered concomitantly with the initial priming dose of carrier protein as well as when the GVH was induced in animals that had been exposed to antigen several days previously. This indicates that the allogeneic enhancing effects can be manifested on either primed or unprimed T cell populations. The ultimate effect of the GVH reaction on the development of helper T cell activity was found to be related to the number of allogeneic cells employed and the duration of the resultant GVH reaction in the carrier-primed host animal. Hence, allogeneic stimulation of slightly greater magnitude and/or longer duration resulted in marked suppression rather than enhancement of helper cell function in such donor mice. These findings may have general relevance to problems in autoimmune diseases and tumor immunity

THE ALLOGENEIC EFFECT IN INBRED MICE : III. UNIQUE ANTIGENIC STRUCTURAL REQUIREMENTS IN THE EXPRESSION OF THE PHENOMENON ON UNPRIMED CELL POPULATIONS IN VIVO

The allogeneic effect has been shown to replace the requirement for carrier-specific helper thymus-derived (T) lymphocytes in secondary antihapten antibody responses in guinea pigs or mice. Attempts to enhance primary antibody responses to either 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH) or DNP-ovalbumin (OVA) by the allogeneic effect have failed, and frequently result in suppression. However, the present studies have demonstrated a clear allogeneic effect on primary anti-DNP responses to a DNP-conjugate of the copolymer of D-glutamic acid and D-lysine, DNP-D-GL. This compound, for which no carrier-specific helper T cells exist, normally induces a state of DNP-specific tolerance in the doses employed. However, normal (BALB/c x A/J)F1 recipients developed primary anti-DNP antibody responses, and of the IgG class, when DNP-D-GL was administered shortly after the transfer of allogeneic parental A strain lymphoid cells. To test the possibility that the presence of KLH-specific T lymphocytes might inhibit the expression of the allogeneic effect on the primary response to DNP-KLH, studies were undertaken using T cell-depleted spleen cells. In this model, the allogeneic effect again enhanced the primary response to DNP-D-GL, but still failed to enhance the primary response to DNP-KLH. These studies indicate that the structure of the molecule employed and its specific interaction with the bone marrow-derived (B) cell membrane may be critical in the capacity of primed and unprimed B cells to be influenced by the allogeneic effect

THE ALLOGENEIC EFFECT IN INBRED MICE : I. EXPERIMENTAL CONDITIONS FOR THE ENHANCEMENT OF HAPTEN-SPECIFIC SECONDARY ANTIBODY RESPONSES BY THE GRAFT-VERSUS-HOST REACTION

The administration of allogeneic lymphoid cells to 2,4-dinitrophenyl keyhole limpet hemocyanin (DNP-KLH)-primed mice prepares such recipients for markedly enhanced secondary anti-DNP antibody responses to a DNP conjugate of a heterologous carrier. This allogeneic effect phenomenon, reflecting the development of a graft-versus-host (GVH) reaction, was first described in guinea pigs and has been extended in the present studies to inbred mice. The expression of the allogeneic effect in mice is dependent upon critical factors such as the number and route of administration of allogeneic cells, the time interval between cell transfer and secondary challenge, and the strength of histocompatibility differences between the donor and the host. The transient GVH reaction established by the transfer of allogeneic cells obviates the requirement for carrier-specific helper T cells in secondary anti-DNP responses, as evidenced by the ability to elicit such responses with DNP-D-GL, a substance which presumably does not stimulate effective T cell helper function. These studies also demonstrate that primed B cells which are not an integral part of the active GVH reaction fail to produce enhanced levels of antibody

The Nature of Lyman Break Galaxies in Cosmological Hydrodynamic Simulations

What type of objects are being detected as $z\sim 3$ "Lyman break galaxies"? Are they predominantly the most massive galaxies at that epoch, or are many of them smaller galaxies undergoing a short-lived burst of merger-induced star formation? We attempt to address this question using high-resolution cosmological hydrodynamic simulations including star formation and feedback. Our $\Lambda$CDM simulation, together with Bruzual-Charlot population synthesis models, reproduces the observed number density and luminosity function of Lyman break galaxies when dust is incorporated. The inclusion of dust is crucial for this agreement. In our simulation, these galaxies are predominantly the most massive objects at this epoch, and have a significant population of older stars. Nevertheless, it is possible that our simulations lack the resolution and requisite physics to produce starbursts, despite having a physical resolution of \la 700 pc at z=3. Thus we cannot rule out merger-induced starburst galaxies also contributing to the observed population of high-redshift objects.Comment: 5 pages, contribution to the Proceedings of Rencontres Internationales de l'IGRAP, Clustering at High Redshift, Marseille 199

Theoretical Modeling of the High Redshift Galaxy Population

We review theoretical approaches to the study of galaxy formation, with emphasis on the role of hydrodynamic simulations in modeling the high redshift galaxy population. We present new predictions for the abundance of star-forming galaxies in the Lambda + cold dark matter model (Omega_m=0.4, Omega_L=0.6), combining results from several simulations to probe a wide range of redshift. At a threshold density of one object per arcmin^2 per unit z, these simulations predict galaxies with star formation rates of 2 msun/yr (z=10), 5 msun/yr (z=8), 20 msun/yr (z=6), 70-100 msun/yr (z=4-2), and 30 msun/yr (z=0.5). For galaxies selected at a fixed comoving space density n=0.003 h^3 Mpc^{-3], a (50 Mpc/h)^3 simulation predicts a galaxy correlation function (r/5 Mpc/h)^{-1.8} in comoving coordinates, essentially independent of redshift from z=4 to z=0.5. Different cosmological models predict global histories of star formation that reflect their overall histories of mass clustering, but robust numerical predictions of the comoving space density of star formation are difficult because the simulations miss the contribution from galaxies below their resolution limit. The LCDM model appears to predict a star formation history with roughly the shape inferred from observations, but it produces too many stars at low redshift, predicting Omega_* ~ 0.015 at z=0. We conclude with a brief discussion of this discrepancy and three others that suggest gaps in our current theory of galaxy formation: small disks, steep central halo profiles, and an excess of low mass dark halos. While these problems could fade as the simulations or observations improve, they could also guide us towards a new understanding of galactic scale star formation, the spectrum of primordial fluctuations, or the nature of dark matter.Comment: 12 pages, 3 figs. To be published in "Photometric Redshifts and High Redshift Galaxies", eds. R. Weymann, L. Storrie-Lombardi, M. Sawicki & R. Brunner, (San Francisco: ASP Conference Series

Automatic Detection of Cone Photoreceptors In Split Detector Adaptive Optics Scanning Light Ophthalmoscope Images

Quantitative analysis of the cone photoreceptor mosaic in the living retina is potentially useful for early diagnosis and prognosis of many ocular diseases. Non-confocal split detector based adaptive optics scanning light ophthalmoscope (AOSLO) imaging reveals the cone photoreceptor inner segment mosaics often not visualized on confocal AOSLO imaging. Despite recent advances in automated cone segmentation algorithms for confocal AOSLO imagery, quantitative analysis of split detector AOSLO images is currently a time-consuming manual process. In this paper, we present the fully automatic adaptive filtering and local detection (AFLD) method for detecting cones in split detector AOSLO images. We validated our algorithm on 80 images from 10 subjects, showing an overall mean Dice’s coefficient of 0.95 (standard deviation 0.03), when comparing our AFLD algorithm to an expert grader. This is comparable to the inter-observer Dice’s coefficient of 0.94 (standard deviation 0.04). To the best of our knowledge, this is the first validated, fully-automated segmentation method which has been applied to split detector AOSLO images

CELL INTERACTIONS BETWEEN HISTOINCOMPATIBLE T AND B LYMPHOCYTES : I. ALLOGENEIC EFFECT BY IRRADIATED HOST T CELLS ON ADOPTIVELY TRANSFERRED HISTOINCOMPATIBLE B LYMPHOCYTES

The adoptive transfer of 2,4-dinitrophenyl(DNP)-keyhole limpet hemocyanin(KLH)-primed lymphocytes into a heavily irradiated allogeneic recipient permits the development of a secondary anti-DNP antibody response to DNP-bovine gamma globulin(BGG) whether or not the irradiated allogeneic host possesses BGG-specific helper T cells. This "allogeneic effect" has been demonstrated to result from the capacity of residual, apparently radioresistant, T cells in the irradiated host to exert an active effect on the transferred histoincompatible B lymphocytes. This conclusion derives from two corroborative experiments. In the first, an allogeneic effect was shown to occur on DNP-primed F1 spleen cells that had been adoptively transferred to irradiated parental recipients; the second experiment demonstrated the development of an allogeneic effect on anti-θ-treated, DNP-specific donor cells transferred to irradiated allogeneic hosts. These results emphasize the extreme caution required in designing and interpreting experiments that may involve adoptive cell transfers into histoincompatible hosts, and illustrate why such models are unsuitable for investigation of the question of physiologic cooperative interactions between T and B lymphocytes. Suitable approaches are described in the accompanying paper

Mean values with cubic characters

We investigate various mean value problems involving order three primitive Dirichlet characters. In particular, we obtain an asymptotic formula for the first moment of central values of the Dirichlet L-functions associated to this family, with a power saving in the error term. We also obtain a large-sieve type result for order three (and six) Dirichlet characters.Comment: 22 pages; greatly shortened, simplified and corrected versio