Cells Of Different Subtypes Research Articles

Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed

Proliferating single cells were isolated from various CNS regions (telencephalon, diencephalon, midbrain, cerebellum, pons and medulla, and spinal cord) of human fetal cadavers at 13 weeks of gestation and grown as neurospheres in long-term cultures. We investigated whether neural stem cells (NSCs) or progenitors within spheres have specific regional or temporal characteristics with regard to growth, differentiation, and region-specific gene expression, and whether these molecular specifications are reversible. Regardless of regional origin, all of the neurospheres were found to contain cells of different subtypes, which suggests that multipotent NSCs, progenitors or radial glial cells co-exist with restricted neuronal or glial progenitors within the neurospheres. Neurospheres from the forebrain grew faster and gave rise to significantly more neurons than did those from either the midbrain or hindbrain, and regional differences in neuronal differentiation appeared to be sustained during long-term passage of neurospheres in culture. There was also a trend towards a reduction in neuronal emergence from the respective neurospheres over time in culture, although the percentages of neurons generated from cerebellum-derived neurospheres increased dramatically. These results suggest that differences in neuronal differentiation for the various neurospheres are spatially and temporally determined. In addition, the properties of glial fibrillary acidic protein (GFAP)-, glutamate-, and gamma-aminobutyric acid (GABA)-expressing cells derived from neurospheres of the respective CNS regions appear to be regionally and temporally different. Isolated human neurospheres from different CNS compartments expressed distinctive molecular markers of regional identity and maintained these patterns of region-specific gene expression during long-term passage in vitro. To determine the potential of human neurospheres for regional fate plasticity, single spheres from the respective regions were co-cultured with embryonic day 16.5 (E16.5 d) mouse brain slices. Specific cues from the developing mouse brain tissues induced the human neurospheres to express different marker genes of regional identity and to suppress the expression of their original marker genes. Thus, even the early regional identities of human neurospheres may not be irreversible and may be altered by local inductive cues. These findings have important implications for understanding the characteristics of growth, differentiation, and molecular specification of human neurospheres derived from the developing CNS, as well as the therapeutic potential for neural repair.

Angioimmunoblastic T cell lymphoma is derived from mature T-helper cells with varying expression and loss of detectable CD4.

Angioimmunoblastic T cell lymphoma (AILT) is a rare lymphoma that is regarded as a clinicopathologic entity but shows considerable histomorphologic diversity, variable immunophenotypes and inconsistent T cell receptor (TCR) gene rearrangement. One hundred four paraffin blocks of AILT were investigated defining tumor cell lineage by triple immunostains with a confocal laser scanning microscope and correlating morphology, immunophenotype and TCRgamma gene rearrangement to clinical outcome. Ninety-nine cases were CD4(+), some of them showing a mixture of CD4(+) and CD4(-) tumor cells. The remaining 5 specimens were CD3(+)/CD4(-)/CD8(-). A considerable number of T cells of different subtypes could always be found, but even in 13 cases predominated by CD8(+) cells, proliferation could be attributed to atypical CD4(+) cells. TCRgamma gene rearrangement was monoclonal in 48 cases (69%) among 70 tested. In 29 of these semi-quantitative gene scan analysis resulted in a median proportion of monoclonal peak of 35% of PCR-products. Clinical outcome was identical grouping patients by clonality of TCRgamma, absence or presence of clear cell clusters and international prognostic index. We conclude that AILT is mainly derived from CD2(+)CD3(+)CD4(+)CD5(+)CD7(-) mature T-helper cells with varying expression and partial loss of detectable CD4. A significant number of non-neoplastic T cells (resting CD4(+) T cells and activated small or medium-sized CD8(+) lymphocytes) may coexist with a minor neoplastic T cell population. Clinicopathologic correlation suggests AILT to be a well defined homogeneous entity with poor prognosis. Currently no prognostic factors can be derived.

Mapping of the keratin polypeptides in meningiomas of different types: An immunohistochemical analysis of 463 cases

Keratins are known to be expressed in some meningiomas, and they have been consistently reported in secretory meningiomas. However, the expression of individual keratin polypeptides has not yet been systematically explored, and such a study could provide important information for the differential diagnosis of meningioma and other tumors, particularly metastatic carcinomas. In this study we analyzed the keratin polypeptide patterns of 463 meningiomas of different types using well-characterized monoclonal antibodies specific to 11 individual keratins and 3 additional antibodies that recognize more than 1 keratin. Archnoid tissues from autopsies were examined for comparison. Secretory meningiomas showed consistent positivity for all simple epithelial keratins K7, K8, K18, and K19, usually limited to the slender spindle cells lining the gland-like lumina. Other keratins variably detected in a minority of gland-like structures were K5/6, K14, K16, and K17. Among other meningiomas, keratin 18 was commonly present in a significant number of tumor cells in different subtypes (30% to 80% of cases), often extensively. The K18 positivity of meningiomas paralleled that observed in normal arachnoids, which were negative for K7, K8, K19, and AE1. Only rare meningiomas, other than the secretory ones, had significant positivity for K7, K8, K19, and other keratins than K18. The concentric spindle cells around psammoma bodies and few other spindle cell foci were often focally positive for K7 and to lesser degree for K8, K14, and K19. The complex pattern of keratins in meningiomas has to be considered in the differential diagnosis of meningioma and metastatic carcinoma. In this context, antibodies to K7, K8, and K19 and the antibodies AE1 and AE3 are useful, because they only rarely label significant numbers of meningioma cells but are positive in a great majority of carcinomas. Careful histologic analysis is necessary to differentiate anaplastic meningiomas and metastatic carcinomas, which have overlapping patterns of several keratins except K20, which was never present in any type of meningioma. HUM PATHOL 33:590-598. This is a US government work. There are no restrictions on its use.

Apoptosis in thymic epithelial tumors.

We studied Fas/FasL, Bcl-2, and M30 CytoDeath in five cases of normal thymus and 41 cases of thymic epithelial tumors (TETs). In normal thymus, Fas was expressed in all epithelial cells, but not in thymic lymphocytes; FasL was weakly expressed only in medullary epithelium and Hassal's corpuscles. In TETs, Fas was expressed in all epithelial cells and lymphocytes, while FasL was differently expressed in epithelial cells of different subtypes of TETs, i.e., type A (2/2), AB (12/12), B1 (0/9), B1/B2 (0/3), B2 (0/1), B2/B3 (1/3), B3 (6/10) and C (1/1), but not in lymphocytes. Bcl2 protein was strongly expressed in medullary-derived lymphocytes of normal thymus and TETs, and weakly expressed only in medullary (spindle) epithelium of TETs. On M30 CytoDeath immunostaining, apoptotic indices were very low in all TETs (0-1.2). In conclusion, since FasL was expressed on the epithelial cells of lymphocyte-depleted (LD) areas of type B2/B3 and/or LD subtypes (type A, AB, B3, C), FasL expression could be relevant for the intracytoplasmic processes of T-cell selection and the regulation of the lymphoid cells inside the tumor, at least partly. However, tumorigenesis of TETs is not necessarily induced by abrogation of apoptosis.

T-cell clonal analysis of HLA-DR2 haplotypes

Individuals carrying the serologically-defined DR2 haplotypes can be further subdivided by utilizing T cell response to define several HLA-Dw/LD clusters: Dw2, Dw12, LD-5a, and a related group composed of FJO, AZH, and MN2. We have used cytotoxic T cell clones generated against these DR2 haplotypes to define the DR and DQ associated Dw/LD polymorphisms. Clones were categorized as DR, DQ, DP, or class 1-directed based on monoclonal antibody (MoAb ∗) inhibition studies. We analyzed the distribution of the determinants detected by these clones based on analysis with panels of cells. Some DR-directed clones only lysed cells positive for the Dw subtype of the sensitizing cell. A few DR-directed clones lysed most DR2 positive cells. Other DR-directed clones detected determinants shared by cells of different subtypes: determinants shared by Dw2 and Dw12 positive cells and determinants shared by MN2, FJO, AZH, and LD-5a positive cells. The majority of the DQ-directed clones only lysed cells positive for the sensitizing HLA-Dw subtype. A group of clones primed against an LD-5a HTC, whose cytolytic activity was not blocked by any monoclonal antibodies tested, lysed some, but not all, DR2 positive cells as well as Dw1 and Dw10 positive cells. The results suggest the detection of determinants on these molecules which may be shared by cells of specific Dw subgroups and determinants shared by most cells of the sensitizing serological specificity. The basis of this observed polymorphism and influence on the allogeneic response are discussed.