SummaryThe T lymphocytes mediating autoimmune destruction of pancreatic [3 cells in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM) may be generated due to functional defects in hematopoietically derived antigen-presenting cells (APC). However, it has not been clear which particular subpopulations ofAPC (B lymphocytes, macrophages, and dendritic cells) contribute to the development and activation of diabetogenic T cells in NOD mice. In the current study we utilized a functionally inactivated immunoglobulin (Ig)l.* allele (Ig/x ''a) to generate a "speed congenic" stock of B lymphocyte-deficient NOD mice that are fixed for linkage markers delineating previously identified diabetes suscepnbility (Ida") genes, These B lymphocyte NOD.Igi.,, ''tt mice had normal numbers of T cells but were free of overt IDDM and insulitis resistant, while the frequency of disease in the B lymphocyte intact segregants was equivalent to that of standard NOD mice in our colony. Thus, B lymphocytes play a heretofore unrecogmzed role that is essential for the initial development and/or activation of [3 cell autoreactive T cells in NOD mice.

This article describes some of the milestones in research concerned with protozoan parasites of the genus Eimeria that infect birds and cause the disease coccidiosis. The time period covered is from 1891, when oocysts were first found in the ceca of diseased chickens, to the present. Progress in our understanding has lagged behind that of other protozoan parasites such as Toxoplasma and Plasmodium despite the enormous importance of Eimeria to animal livestock production. Nevertheless, applied research by universities, government agencies, and private industry has resulted in the successful development of methods of control, research that continues today. The topics covered and the references provided are selective and include life cycles and biology, pathology, ultrastructure, biochemistry, immunity, genetics, host cell invasion, species identification, taxonomy, chemotherapy, vaccination, and literature concerned with avian coccidiosis. This review is primarily concerned with the avian species of Eimeria that infect poultry, but some important advances, principally in immunology, have been made using species that infect rodents and rabbits. These are included where appropriate.

In July 1971, the polyether ionophorous antibiotic monensin was introduced in the United States for the control of coccidiosis in poultry. At that time, prospects for new anticoccidial agents were not good. Amprolium had enjoyed several years of use, but many other compounds had been abandoned as resistance to them developed. After the introduction of monensin, most commercial broilers were medicated with the drug and it is still widely used for this purpose today. Apart from in poultry, monensin is also used to control coccidiosis in game birds, sheep, and cattle. Indeed, more animals have been medicated with ionophores, such as monensin, for control of disease than any other medicinal agents in the history of veterinary medicine. In this review, we discuss the discovery, mode of action, and efficacy of monensin, together with matters of importance to the poultry industry such as commercial use, drug resistance, toxicity, pharmacology and residues, host immunity to coccidiosis, and effects in other avian species.

Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic ␤ cells. Although both major histocompatibility complex class I-restricted CD8؉ and class II-restricted CD4 ؉ T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic CD8؉ T cells responsible, we isolated and propagated in vitro CD8 ؉ T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-2K d , and showed a diverse T cell receptor ␤ chain repertoire. In contrast, their ␣ chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of V␣17 family members frequently joined to the J␣42 gene segment. These results suggest that a number of the CD8 ؉ T cells participating in the initial phase of autoimmune ␤ cell destruction recognize a common structural component of K d ͞peptide complexes on pancreatic ␤ cells, possibly a single peptide.Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by T cell-mediated destruction of pancreatic islet ␤ cells (1). The nonobese diabetic (NOD) mouse (2) constitutes a widely studied model system for IDDM, as it shares many of the characteristics of the human disease. For example, human patients and NOD mice both develop lymphocytic infiltration of islets (insulitis) and subsequent ␤ cell destruction mediated by T lymphocytes. Cell-surface ␣␤ T cell receptors (TCRs) enable such T lymphocytes to recognize specific antigens on the surfaces of target cells in the form of peptides complexed with major histocompatibility complex (MHC) molecules, with CD8 ϩ cytotoxic T lymphocytes being restricted to class I MHC molecules and CD4 ϩ T cells to class II.Certain unusual MHC class II alleles provide the strongest genetic component of IDDM susceptibility in both humans and NOD mice (3). Thus, it is not surprising that autoreactive CD4 haplotype (15). However, although the requirement for CD8 ϩ T cells in IDDM development is clear, whether they are only needed to initiate the earliest events of ␤ cell destruction or are critical to all stages of diabetogenesis remained unknown and is one of the questions addressed in this study.It is also necessary to define the characteristics and specificities of MHC class I-restricted effectors participating in the earliest initiative phases of IDDM. In view of the importance of understanding the nature of these initiating T cells, we have developed a technique for the isolation of monoclonal and oligoclonal populations of NOD ␤ cell-cytotoxic CD8 ϩ T cells that uses islets from a newly developed stock of NODscid.RIPB7 mice as a potent source of stimulating antigen. This approach has enabled us to isolate cytotoxic CD8 ϩ T cells from pred...