cells mainly are in the circulation (5-15% of the circulating lymphocytes) yet are also distributed in tissues everywhere. lak cells (lymphokine-activated killer) are a laboratory/clinical subset of nk cells promoted by il-2 to attack tumor cells. nkt cells see natural killer t cell main article natural killer t cells. human nk t cells are a unique population (which express nk cell markers such as cd56 and kir). nkt cells are thought to play an important role in tumor immunity and immunoregulation. (medical immunology, p. 135), yet little is known. recent evidence suggests a role working together with hepatic stellate cells being a liver-resident antigen-presenting cell that presents lipid antigens to and stimulates proliferation of nkt cells. natural killer-like t cells a heterogeneous group with ill-defined properties. however, in summary there is no known cell or set of cells that is capable of killing cancerous cells in general. labeling lymphopoiesis because all wbcs are microscopic, colorless and often seemingly identical in appearance they are individually identified by their natural chemical markers, many of which have been analyzed and named. when two cells have the same markers, the reasonable assumption is made that the cells are identical at that time. a set of markers is colloquially described as the barcode for that cell or that cell line. here is an example of how a barcode can come to be, for the all-important hematopoietic stem cell (hsc) as an example. hscs are technically described as: lacking fms-like tyrosine kinase 3 (flt3) and lacking the markers specific to discrete lymphoid lineages (lin), but expressing high levels of sca1 and c-kit; hsc also express cd44, low levels of thy1.1 (cd90), but no il-7ra or cd27. this is called the (surface) phenotype of an hsc. it can be expressed as a set (lin2, sca1high, c-kit high, cd44+, thy1.1low, cd27 2, and il-7ra2). this set is a ‘barcode’ for the hsc, akin to the barcode label attached to your chicken-wing plastic bag for checkout at a supermarket! scientists use these barcodes to check, categorize and accumulate cells for many purposes often using laboratory methods such as cell flow cytometry. these barcodes partially define the modern meaning of phenotype for leukocytes. progression of hsc differentiation and lineage commitment is indicated by changes in this phenotype. that is, as the cell changes, the markers will also change and the barcode will change. typical barcodes for some cell types appearing in this article. cell type barcode etp c-kit+, cd44+, cd25- dn1 cd44+, cd25- dn2 cd44+, cd25+ note explaining the barcode parameter details: flt3 is a cytokine tyrosine kinase receptor thought to be important in early lymphoid development. in addition, flt3 plays a major role in maintaining b lymphoid progenitors. cd27 plays a role in lymphoid proliferation, differentiation, and apoptosis. the acquisition of cd27 and flt3 by the hsc coincides with the loss of long-term repopulating potential. at this stage the cells retain both lymphoid and myeloid potential and are referred to as multipotent progenitors. (medical immunology, p. 114) knowledge development regarding lymphopoiesis new questions emerge in immunology continuously as though there were a stem cell for questions. for example, it was thought that the process of lymphopoiesis was a direct, orderly unidirectional sequence. but it is not clear if end-stage lymphocytes come from progenitors that are homogeneous populations or overlapping populations. nor is it clear whether lineages of lymphocytes develop via a continuum of differentiation with a progressive loss of lineage options or whether abrupt events result in the acquisition of certain properties. changes in cytoplasm, morphology of the cell nucleus, granules, cell internal biochemistry, signaling molecules and cell surface markers are difficult to correlate with definite stages in lymphopoiesis. the morphological differences do not just correspond to steps in mitosis (somatic cell division), but result from continuous "maturation processes"of the cell nucleus as well as of the cytoplasm and so one must not be too rigid about morphological distinctions between certain cell stages. models and updates on the lymphopoiesis family tree until recently the model of the cmp generating all myeloid cell and the clp generating all lymphoid cells was considered necessary and sufficient to explain the known facts observed in the generation of wbcs, and it is still found in most basic textbooks. however beginning around 2000 and gaining momentum after 2005 in both studies in humans and mice, new complexities were noted and published in papers. these studies are important now mainly to immunology researchers but are likely to eventually lead to changes in medical treatments. the changes were sparked by observations that lymphopoiesis did not always break into two lineages at the level of the clp. worse, some macrophages (long considered a myeloid lineage) could be generated by lymphoid lineage progenitors. in essence focus has been shifted away from the clp to the mlp (lymphoid-specified progenitors), which are clearly lymphoid progenitors yet retain some myeloid potential, particularly the ability in both humans and mice to make macrophages - one of the most versatile of immune cell defenders - and also many dendritic cells, the best 'watchdogs' of antigen invaders. however, whatever the details may turn out to be, the process of lymphopoiesis always seems to relentlessly give rise to progeny with special attributes and abilities - "superpowers" so to speak - but with progressively more restricted lymphoid developmental potential. stages of development the old model: lymphoid vs myeloid this model of lymphopoiesis had the virtue of relative simplicity, agreement with nomenclature and terminology, and is still essentially valid for the laboratory mouse. phsc pluripotent, self-renewing, hematopoietic stem cells which give rise to mpp multipotent progenitors, which give rise to elp (or pro) prolymphocytes, early lymphoid progenitors, and finally to the clp common lymphoid progenitor, a cell type fully committed to the lymphoid lineage. phsc, mpp and elp cells are not fully committed to the lymphoid lineage because if one is removed to a different location it may differentiate into non-lymphoid progeny. however clp are committed to the lymphoid lineage. the clp is the transit cell responsible for these (generally parallel) stages of development, below: nk cells dendritic cells (lymphoid lineage; dc2 ) progenitor b cells pro-b cells => early pro (or pre-pre)-b cells => late pro (or pre-pre)-b cells large pre-b cells => small pre-b cells immature b cells b cells => (b1 cells; b2 cells) plasma cells pro-t cells t-cells research on new models (not mice) by 2008 it was found that "the majority of early thymic progenitor cells do not commit to becoming t cells by the time they get to the thymus gland. etp cells retained the ability to become either t cells or myeloid cells."