Prevalence Of Memory Research Articles

The ISCCA flow protocol for the monitoring of anti-CD20 therapies in autoimmune disorders.

Anti-CD20 monoclonals (MoAbs) are used in a variety of autoimmune disorders. The aim is to eliminate memory B cells sustaining the tissue damage and the production of pathogenic autoantibodies, while preserving naïve cells. The disappearance of memory B cells and the repopulation by naïve cells correlate with good clinical response, while the reappearance of memory B cells and plasmablasts correlates with relapse or resistance to therapy. Anti-CD20 induce extremely low B cell levels, requiring high-resolution techniques. The immune monitoring protocol developed by ISCCA is described and validated, to provide a standardized method for the clinical decision-making process during anti-CD20 therapies in autoimmune diseases. A 10-marker, 8-color staining panel (CD20-V450, CD45-V500c, CD4-FITC + sIgM-FITC, CD38-PE, CD3-PerCP Cy5.5, CD19-PE-Cy7, CD27-APC, CD8-APC H7 + sIgG-APC-H7) is used to identify B cells, plasma cells/blasts, naïve and memory B cells, sIgM+ and sIgG-switched memory B cells, T and NK cells, with high-sensitivity analysis (>106 CD45+ cells). After an anti-CD20 dose, the B cell level is about zero in most patients. If B cells remain virtually absent (<0.1/μl), subsetting is not reliable nor meaningful. If B cells raise >0.3-0.5/μl, subsetting is possible and informative, acquiring >1.0-1.5 × 106 CD45+ events. Further testings can follow the quality of B cell repopulation. If B cells become detectable (>1/μl), the prevalence of memory B cells indicates non-responsiveness or a possible relapse. The ISCCA Protocol is proposed for a standardized prospective monitoring of patients with autoimmune disorders, to assist the safe and rational usage of anti-CD20 therapies.

Prevalence of Intracellular Galectin-1-Expressing Lymphocytes in Umbilical Cord Blood in Comparison with Adult Peripheral Blood

Umbilical cord blood (UCB) is a promising alternative for the treatment of hematological malignancies. The lower immune reactivity of UCB lymphocytes is a well-known phenomenon; however, immune tolerance mechanisms are not fully elucidated. Galectin-1 has strong immunosuppressive properties and plays a key role in the regulation of immune reactivity. We aimed to determine the properties of intracellular galectin-1 (Gal-1)-producing cells within CD3, CD4, CD8, regulatory T (Treg), and natural killer (NK) cells in UCB compared to adult peripheral blood (APB). We took peripheral blood samples from 22 healthy adults and cord blood samples from 19 healthy, term neonates. Intracellular Gal-1 expression was determined by flow cytometry in the above subsets. Furthermore, we assessed the prevalence of naive and memory T cells that play a role in the regulation of immune reactivity. We also performed functional analyses to assess the effect of exogenous Gal-1 on the rate of proliferation of T lymphocytes isolated from APB and UCB. The prevalence of intracellular Gal-1-expressing CD3, CD4, CD8, Treg and NK lymphocytes was lower in UCB than in APB. However, their capability to produce Gal-1 reaches the level seen in adults. The prevalence of naive cells was higher, whereas that of central and effector memory T cells was lower in UCB compared with APB. Lower Gal-1-producing cell proportion might be due to the naivety of neonatal lymphocytes, as indicated by the positive correlation detected between the number of CD3 lymphocytes expressing intracellular Gal-1 and the prevalence of memory T cells. The intracellular expression of Gal-1 may be down-regulated in neonatal lymphocytes due to the already reduced immune reactivity of UCB. In contrast with previous findings, our results indicate that the administration of exogenous Gal-1 failed to decrease the rate of proliferation in T lymphocytes isolated from either APB or UCB. This suggests that Gal-1-expressing lymphocytes are unlikely to play a major role in mitigating the immune reactivity of UCB.

Memory T-Cell Predominance Following T-Cell Depletional Therapy Derives from Homeostatic Expansion of Naive T Cells

T-cell depletion reportedly leads to alterations in the T-cell compartment with predominant survival of memory phenotype CD4 T cells. Here, we asked whether the prevalence of memory T cells postdepletion results from their inherent resistance to depletion and/or to the homeostatic expansion of naive T cells and their phenotypic conversion to memory, which is known to occur in lymphopenic conditions. Using a 'mosaic memory' mouse model with trackable populations of alloreactive memory T cells, we found that treatment with murine antithymocyte globulin (mATG) or antilymphocyte serum (ALS) effectively depleted alloreactive memory CD4 T cells, followed by rapid homeostatic proliferation of endogenous CD4 T cells peaking at 4 days postdepletion, with no homeostatic advantage to the antigen-specific memory population. Interestingly, naive (CD44lo) CD4 T cells exhibited the greatest increase in homeostatic proliferation following mATG treatment, divided more extensively compared to memory (CD44hi) CD4 T cells and converted to a memory phenotype. Our results provide novel evidence that memory CD4 T cells are susceptible to lymphodepletion and that the postdepletional T-cell compartment is repopulated to a significant extent by homeostatically expanded naive T cells in a mouse model, with important important implications for immune alterations triggered by induction therapy.

The ‘ghosts’ that pester studies on learning in mosquitoes: guidelines to chase them off

The identification of memory and learning in medically important mosquito species has been of epidemiological interest mainly because of the implications of learning on the pattern of contact between vectors and hosts. Empirical results either showing or suggesting the existence of cognitive abilities in mosquitoes have been reported in a number of experimental studies, mainly based on the observation of individual fidelity towards subsets of specific resources, such as hosts, resting sites or breeding sites. A closer inspection of the design of these experiments shows that, with the exception of recent studies providing stronger evidence of learning in the genus Culex (Diptera: Culicidae), methodological shortcomings still hinder the possibility of eliminating alternative interpretations for these findings, in some cases because the experiments were not specifically designed to identify the phenomenon, but mostly because of a lack of appropriate controls or replication. By highlighting these limitations, while acknowledging the practical difficulties that are inherent to the field, we aim to help expel from future research the 'ghosts' that still preclude the achievement of more definite conclusions about the prevalence of memory and learning in this group of insects.

A previously unrecognized H-2D(b)-restricted peptide prominent in the primary influenza A virus-specific CD8(+) T-cell response is much less apparent following secondary challenge.

Respiratory challenge of H-2(b) mice with an H3N2 influenza A virus causes an acute, transient pneumonitis characterized by the massive infiltration of CD8(+) T lymphocytes. The inflammatory process monitored by quantitative analysis of lymphocyte populations recovered by bronchoalveolar lavage is greatly enhanced by prior exposure to an H1N1 virus, with the recall of cross-reactive CD8(+)-T-cell memory leading to more rapid clearance of the infection from the lungs. The predominant epitope recognized by the influenza virus-specific CD8(+) set has long been thought to be a nucleoprotein (NP(366-374)) presented by H-2D(b) (D(b)NP(366)). This continues to be true for the secondary H3N2-->H1N1 challenge but can no longer be considered the case for the primary response to either virus. Quantitative analysis based on intracellular staining for gamma interferon has shown that the polymerase 2 protein (PA(224-233)) provides a previously undetected epitope (D(b)PA(224)) that is at least as prominent as D(b)NP(366) during the first 10 days following primary exposure to either the H3N2 or H1N1 virus. The response to D(b)NP(366) seems to continue for longer, even when infectious virus can no longer be detected, but there is no obvious difference in the prevalence of memory T cells specific for D(b)NP(366) and D(b)PA(224). The generalization that the magnitude of the functional memory T-cell pool is a direct consequence of the clonal burst size during the primary response may no longer be useful. Previous CD8(+)-T-cell immunodominance heirarchies defined largely by cytotoxic T-lymphocyte assays may need to be revised.