Relation between Blood Lymphocytes and Total Body Lymphocytes

Naive and effector/memory T cells have distinct repertoires of trafficking ligands and receptors that restrict their ability to interact with specialized microvessels in different anatomical compartments and, consequently, have distinct patterns of migration. Antigen-experienced lymphocytes can be further subdivided into different subsets based on their expression of characteristic sets of trafficking receptors that favor their accumulation in certain target organs, including the skin and gut. Here, we summarize recent advances that have broadened our understanding of the cellular and molecular events that induce the generation of tissue-specific effector/memory T cells and discuss how these mechanisms could be harnessed for the therapeutic manipulation of T-cell-dependent pathologies. Free Full Text: http://labs.idi.harvard.edu/vonandrian/Pages/Mora_TI27_235_0506.pdf (ii) Secondly, lymphocytes are not a single cell type. The trials remove monocytes and all 3 major types of lymphocyte; natural killer cells, B cells and T cells. To pick just one of these, T cells come in two varieties; helper (CD4+ regulatory) T cells and killer (CD8+ cytotoxic) T cells, and each of these has a naïve form and an activated form with very different functions. Memory cells have other subtypes yet again with differing functions. And most importantly, T-cells are each specific for one of millions of different T-cell receptors. While 2% of all lymphocytes may be in the blood circulation at a given time, we know little about the relative distributions of these subtypes beneath the umbrella term “lymphocyte”. What little we do know shows that functionally important subtypes, like naïve T cells, are certainly not evenly distributed. (B) Interventional Experiments Lymphapheresis was tested as a potential therapy for arthritis, on the theory that the symptoms resulting from this erroneous self-targeted immune attack would be alleviated by removing the offending lymphocytes. These studies clearly demonstrate that very few of the body’s “other 98%” of lymphocytes are capable of migration and can contribute to the repopulation of the blood after its depletion. “Lymphocyte depletion by continuous flow cell centrifugation in rheumatoid arthritis” Karsh et al., United States NIH Arthritis and Rheumatism, 1979 22(10):1055-9 Four patients with active, severe arthritis were subjected to lymphapheresis 2 or 3 times weekly for 6 weeks. Excluding Patient 2 (who was lymphopenic at the start of the study), a mean total of 125 x 10 lymphocytes were removed from each patient over the 6 weeks.  Since total body lymphocytes are approximately 500x10, this study removed 25% of this total.  If the body’s lymphocytes were able to migrate freely, several weeks after treatment (assuming no replication), the remaining lymphocytes would have equilibrated to 75% of their original levels.  Yet we know that significant replication would occur to replace lost cells: throughout the 6 weeks of apheresis and the 3-4 subsequent weeks. If one third of the residual lymphocytes replicated just once, or if just 8% of them underwent 3 rounds of division, then original lymphocyte numbers would be fully restored. Results: The lymphocytopenia which developed in these 3 patients persisted at least 3-4 weeks after the end of apheresis: circulating blood lymphocytes were at just 32% of their original levels. Conclusions*: This study shows that lymphocytes are limited in either their ability or ‘inclination’ to equilibrate throughout the body, and suggests that most lymphocytes cannot readily migrate to the blood in response to active depletion of this compartment. * There is no evidence to suggest that lymphocyte migration patterns in arthritis patients are dramatically different from healthy adults. This and several similar studies demonstrate the practical consequences of the lymphocyte tissue restrictions summarized in the review by Mora et al. It would be erroneous to conflate the countless lymphocytes subtypes residing in distinct tissues as though they were a single pool. That they are “only 2% of the body’s total” is of no relevance when considering the consequences of repeatedly removing 80-100% of the blood’s lymphocytes. “Lymphocyte numbers and subsets in the human blood: Do they mirror the situation in all organs?” Blum KS, Pabst R. Hannover Medical School, Germany Immunol Lett. 2007 108(1):45-51. The most direct studies of mammalian blood lymphocyte kinetics have been performed in sheep, given the ethical unviability of human experimentation. The studies found that beside the classical differentiation in T, B and NK cells, blood lymphocytes can be further distinguished according to their migration pattern. The results, illustrated above, showed that 60% of blood lymphocytes belong to the “recirculating lymphocyte pool”, which is characterized by the ability of the cells to exit the blood system and circulate through the lymph system back into the blood. The 40% of blood lymphocytes in the “non-recirculating pool” do not possess this ability. Whether the subtypes of these restricted lymphocytes have particular functional competencies is not known. After repeatedly removing 95% of them with minimal replacement, it is unclear where their particular set of characteristics could be found for repopulation, or whether replication of recirculating lymphocytes would simply replace them. Such an intervention would clearly change the composition of the lymphocytes in the blood after repopulation for a prolonged time. The lymph contains mostly cells of the recirculating lymphocyte pool. About 85% of the cells in the thoracic duct entered the lymph system from the blood and only about 15% of the cells of the lymph enter this system via the afferent lymphatic vessels. Abstract Lymphocyte numbers in the blood are used to evaluate the immune status on a daily basis in medicine. Several studies have documented the normal ranges of lymphocytes and lymphocyte subsets in the peripheral blood. A variety of techniques and criteria have revealed clear differences between the lymphocyte subsets in childhood and adolescence. Race and gender are also variables for blood lymphocytes, and even environmental factors seem to influence the numbers of some lymphocyte populations. However, do all these variations in lymphocyte subsets in the peripheral blood mirror changes in the lymphocyte populations of the whole body, or is it just a result of different migratory habits of cells? The factors influencing the distribution of lymphocytes in the peripheral blood with regard to the different abilities of T and B cells to migrate to distinct lymphoid or non-lymphoid tissue are summarized. In addition it will be described how the removal of organs (e.g. thymus, spleen, liver) influences the distribution of lymphocytes in the blood. All these parameters should be considered not only in the clinical situation when the immune status of a patient is extrapolated from the lymphocyte numbers in the blood, but also when interpreting treatment effects in patients. http://www.sciencedirect.com/science/article/pii/S0165247806002380