Jean-Pierre Bergerat

Comparative study of autologous, total E and ‘active’ E-rosette-forming T lymphocytes in untreated Hodgkin's disease

SummaryIn order to evaluate the value of autologous rosettes, a marker for a T lymphocyte subpopulation, in the diagnosis of T lymphocyte defects, we compared the ability of T cells from untreated patients with Hodgkins disease to form autologous, total E and ‘active’ E rosettes. While the mean percentage of total E and ‘active’ E rosettes was significantly decreased in the patients compared to normal controls (0.01<P<0.02), no difference was observed for autologous rosettes (0.6<P<0.7). Only two patients showed decreased ‘active’ E rosettes whilst eight had decreased total E rosettes. Individual data in the patients showed a wide dispersion of autologous rosettes with both high and low percentages whatever the relative number of the two other T cell markers. No correlation was observed between any of the three types of rosettes in the patients whereas autologous rosettes were clearly correlated with total E (0.01<P<0.02) but not with ‘active’ rosettes in normal controls. Neither autologous nor ‘active’ rosettes could be correlated with skin test results.

Expression of HLA antigens on leukaemia cells.

Virus infected cells can carry HLA antigens not demonstrated in uninfected cells. In a wider context, it is known that tumour cells in the mouse can exhibit H2‐like antigens of foreign haplotypes which they resemble. Our aim was to investigate, using an absorption method, the HLA antigens of ten leukaemic cells and to compare these results with those of normal lymphocytes. The following sera was used for absorption: anti‐B5 serum, anti‐B7 serum, anti‐B12 serum. These sera were absorbed on the ten leukaemic cells and fifteen healthy lymphocytes. An anti‐A1 + B8 serum and an anti‐A2 serum were absorbed on the ten leukaemic cells, but there was not enough serum to carry out the similar absorption with the healthy lymphocytes. Two points emerged from these results. (1) Leukaemia cells absorbed anti‐HLA antibodies as effectively as healthy lymphocytes when the cells carried the antigen corresponding to the serum specificity. The curves obtained with leukaemia cells were comparable to those of healthy cells. (2) When the cells were not carriers of the antigens corresponding to the antibodys specificity, leukaemia cells were also capable of absorbing antibodies, unlike healthy lymphocytes which had no or poor absorption.

Constitutively Active Androgen Receptor Variant Detected in a Human Prostate Cancer

Human androgen receptor (AR) mutation is a possible alternative used by prostate adenocarcinoma (PCA) cells to escape androgen dependence. These mutations may broaden the specificity and/or the sensitivity of the AR to other hormones, resulting in the inappropriate receptor activation, and thus, affecting the PCA response to hormonal therapies. We have developed a yeast-based functional assay to detect mutant ARs in PCA by analyzing their transactivation capacities in response to different ligands. We report herein the detection of two different mutant ARs within the same metastatic tumor sample. Concomitantly to the T877A mutant AR, we identified an additional double mutant AR harboring the nonsense mutation Q640Stop, just downstream of the DNA binding domain together with the T877A point mutation. This mutation leads to a C-terminal truncated AR. This study is the first description of this type of mutation in PCA. We demonstrated that this truncated AR exhibited constitutive transactivation properties. In conclusion, our data suggest that mutation-induced constitutive activation of the AR may be an alternative mechanism used by PCA cells to escape androgen deprivation.

Membrane markers, karyotypic abnormalities, ultrastructure and functional properties of lymphocytes in a case of ‘D-cell’ chronic lymphatic leukemia

D cells are lymphocytes bearing both receptors for the third complement component and the ability to form spontaneous rosettes with SRBC. We report the case of a patient with a D-cell chronic lymphatic leukemia who presented a long evolution without treatment and whose leukemic cell characteristics have been extensively studied. Cytogenetic analysis showed numerous karyotypic abnormalities among leukemic cells; all metaphases were hypodiploid and arranged in four different clones; seven marker chromosomes were present. The cells were found to bear human T-cell specific antigen, the T helper/inducer phenotype, HLA-A and HLA-B determinants, but no HLA-DR antigens. They displayed a high proliferative response to PHA and Con A, no response to PWM stimulation, and possibly the capacity of allogeneic stimulation in the mixed lymphocyte culture system. Assays for cell-mediated cytotoxicity in the CML system, and for K and NK activities were negative.