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J Dausset

Publications and source records attributed to J Dausset.

At least 199 records · Page 11Linked to original sources

[Kinetics of the appearance of HLA-DR antigens on human alloactivated T lymphocytes and the demonstration of new antigenic determinants].

By studying serologically the appearance of HLA-DR determinants on T lymphocytes activated by a mixed lymphocyte culture, we have been able to demonstrate the existence of a new class of antigenic determinants distinct from classical HLA-DR antigens. Indeed, some monospecific anti-DR sera were cytotoxic from some alloactivated T cells, though not directed against their HLA-DR specificity. The absorption of these anti-sera on B lymphocytes bearing the HLA-DR antigen against which they were directed, did not remove their reactivity on alloactivated T lymphocytes. The absorption of the same anti-sera on activated T lymphocytes did not affect their anti-DR reactivity. This study shows the existence of new antigenic determinants expressed by T lymphocytes during their activation: alloactivated T lymphocyte antigens (AATL).

Cells, Cultured↗

[Mode of action of a soluble restricted factor, a suppressor of the allogeneic proliferative response in man].

Appearance of "suppressor cells" is induced by in vitro hyperimmunization of lymphocytes against allogeneic cells, incompatible for one HLA-DR antigen. These "suppressor cells under certain conditions, release in the culture medium, "suppressor factors" of the in vitro allogeneic proliferative response in Man. They are not immunoglobulins and act in a non specific way towards the stimulators. Only one of them is restricted to some individuals. This is shown when either responders or stimulators are incubated for different periods, with the "suppressor factors" prior to the primary mixed lymphocyte reaction (MLRI). The beneficial effect of transfusions on kidney graft survival, could be, in part, explained by a suppressor mechanism, analogous to the one described in vitro.

Cell Division↗

Suppression of the human allogenetic response in vitro with primed lymphocytes and suppressive supernates.

Human lymphocytes primed in vitro by allogeneic cells develop lymphocyte populations with different functions. Cells with a memory of the allogeneic contact and cytotoxic effectors have been identified previously. We now report on a third lymphocyte population generated by repeated in vitro sensitization. This is of suppressor lymphocytes that can inhibit the primary proliferation of unsensitized lymphocytes. Our experiments indicate that these human suppressor cells are most probably T lymphocytes, adherent to glass or nylon wool, and radioresistant. They derive from both the large blast cells and the small, nondividing lymphocytes that are observed on day 7 of the allogeneic response. The suppressor cells release suppressor factor(s) upon restimulation. Studies on the specificity of the suppression have shown that suppressor cells are specific to the HLA-DR antigens presented by stimulator lymphocytes and that they probably release the suppressor factor only when confronted with the specific HLA-DR antigen. However, when the suppressor factor is produced, the proliferative response to any stimulating cell is inhibited regardless of its HLA-DR antigens. On the other hand, the suppressor factor can only suppress the proliferation of lymphocytes from some individuals. This restriction suggests that suppression can only occur when the producer of the suppressor factor and the responding lymphocytes that are being tested, have some identities in common. No evidence in favor of an HLA-D restriction has been obtained so far.

Cell Adhesion↗

An antigen shared by a human T cell subset and B cell chronic lymphocytic leukemic cells. Distribution on normal and malignant lymphoid cells.

We obtained a monoclonal antibody, A50, after immunizing Biozzi's high responder strain of mice with T cell chronic lymphocytic leukemia (T-CLL) cells. A50 recognized an antigen present on the surface of B cell chronic lymphocytic leukemia cells from many patients and from cells of T lineage from any subject we tested. We could not find this antigen either on the surface of normal B cell or on other non-T cell malignancies. On T cells, this antigen was present on a subpopulation of thymus cells, and on most peripheral T cells. The antigen was present on the surface of cells from T-CLL, Sézary's disease, and a subset o T cell lymphoma. The antigen seemed to belong to a complex set of antigenic determinants that we had defined with rabbit antisera.

Animals↗

Is the MHC a general self-recognition system playing a major unifying role in an organism?

From the review of several recent observations of cell-cell interactions, which occur preferentially in autologous or syngeneic situations such as rosettes, adhesion, homing, and contact inhibition, the existence of an active general process of cellular self-recognition, not limited to the immune system, is postulated. This process is MHC associated or dependent, and seems to require an identity of ubiquitous molecules of class I--or other linked gene products at the surface of interacting cells. In contrast, class II molecules are not apparently implicated in general self-recognition. The immune system is regarded as a late evolution from a self-recognition system. It retains the ability of self-evolution, but possesses the exclusive property of active discrimination against foreignness. The astonishing fact that identity of MHC products seems to be needed for recognition is discussed in the context of various possible mechanisms. From immunological and genetical consideration, it is proposed that the genuine biological role of the MHC would be that of a self-recognition and unifying system.

Animals↗

Functional study and detection of HLA-D products on fractionated human bone marrow cells.

Bone marrow cells from nine normal human volunteers obtained from the Iliac crest, were used in this work for antigen determination and functional studies. The bone marrow aspirated cells were sequentially separated: elimination of erythrocyte, granulocytes and monocytes achieved by Ficoll-Isopaque centrifugation followed by plastic adherence. Purified bone marrow cells were finally separated by size using velocity sedimentation. The slow sedimenting small cells were shown to be mainly T lymphocytes, probably of blood origin. The medium sized bone marrow cells were shown to contain myeloid precursors (CFu-c). Large immature cells were in cycle actively synthesizing DNA molecules. HLA-D and HLA-DR detections on the fractionated cells were performed using three techniques: fluorescence with specific anti HLA-DR allo and xeno antisera; primed lymphocyte typing (PLT) with anti HLA-DR monospecific in vitro primed lymphocytes and detection of the HLA-D stimulating product using the bone marrow fractionated cells as stimulators in a mixed leukocyte culture. Concordant results were obtained with the three techniques. Lymphocytes in the bone marrow express HLA-D products a peripheral lymphocytes. Bone marrow fractions depleted of lymphocytes and monocytes also contain approximately 20% of cells expressing HLA-D products The meaning of the expression of HLA-D products on immature precursors non-lymphoid cells is discussed.

Bone Marrow Cells↗

An immunochemical study of the lymphocyte A, Atri system.

The anti-Atri lymphocytotoxic antibodies reacting only with 5.19% of A, ABH-secreting individuals have been tested by an inhibition assay with 19 oligosaccharidic structures carrying the A, B, H or Lewis structures. The inhibitions observed dissociate the A and H blood group substances from the Atri substance, and seem to indicate the role of fucosyl residues, particularly that of fucosyl alpha (1 leads to 3), which may be the immunodominant of the Atri substance.

ABO Blood-Group System↗

Different stimulating capacity of B and T lymphocytes in primary and secondary allogeneic reactions: cellular detection of HLA-D products on T lymphocytes.

The present study was undertaken to define the best way to produce and to test primed lymphocyte typing (PLT) cells using B- and T-enriched lymphocyte suspensions. Intrafamilial PLT cells were produced with primed unseparated and T purified lymphocytes against haplo-identical donors' T and B cells. These PLT cells were then restimulated with a panel of related or unrelated individuals' T and B cells and with allogeneic in vitro activated T cells. The best discrimination was obtained when PLT reagents, regardless of the production method, were restimulated by a B-enriched population of peripheral lymphocytes. Furthermore, the results have shown that enriched primed or unprimed T cell suspensions stimulated by enriched T lymphocytes did not give any proliferation. Experiments performed to explain the results led us to distinguish 2 different phenomena: in primary cultures, the addition of monocytes autologous to the responder cell restored the proliferation of enriched T cells stimulated by T lymphocytes. In secondary cultures, the addition of monocytes autologous to the PLT cell did not restore the proliferation of PLT lymphocytes stimulated by enriched T cells. This was shown to be due to the lack of Dr antigen on the stimulating cell: if allogeneically activated T cells were used as stimulating lymphocytes, a DR-specific proliferative response appeared. This correlates with serologic findings were DR determinants are found on activated T cells and not on unprimed T lymphocytes. However, this difference might be only quantitative, since peripheral lymphocytes could be primed by T cells and be DR specifically restimulated.

B-Lymphocytes↗

[Demonstration of a soluble factor capable of inhibiting allogenic lymphocyte proliferation in man].

During the secondary mixed lymphocyte reaction (MLR), i.e. after the double in vitro allogenic sensitization between responding and stimulating cells bearing at least one HLA-DR incompatibility, suppressor cells are developed [1]. They are able to inhibit a primary MLR provided that the stimulating cells possess the same DR incompatibility as the immunizing cells. We report here that this inhibition is due to the production by these cells of a soluble suppressor factor which acts on responding cells provided that they share at least one gene product of the HLA-D region with the cells producing the factor. This a feedback process of auto-inhibition occurring after hyperimmunization. The action of this suppressor factor seems to be genetically restricted to an as yet unknown locus in linkage disequilibrium with HLA-DR.

Cell Division↗

A simulation of HLA-DR matching in kidney transplantation.

A simulation of the matching for HLA-DR, B, A loci was achieved by taking into account the practical situation of kidney transplants for 89 donors and 322 potential recipients. A complete HLA-DR identical graft was theoretically possible in 52% of the cases. Conversely, if the identity for B or particularly the identities for both B and A were sought, the necessary pool of recipients would have to be much larger, requiring intense international cooperation.

ABO Blood-Group System↗

Role of Ia-like products of the main histocompatibility complex in conditioning skin allograft survival in man.

This report correlates the survival time of 93 intrafamilial skin allografts performed under conditions of main histocompatibility complex (HLA) haploidentity with donor-recipient compatibility for products of the HLA-A, -B, -C, and -DR, as well as C3 proactivator, Glyoxalase I, and P loci located on the human 6th chromosome. Incompatibilities for HLA-A and -B (and to a lesser extent for HLA-C) and(or) for HLA-DR products exerted a strong influence upon the fate of skin allografts. When HLA-A and -B were considered alone, the most compatible group of grafts had a mean survival time of 15.8 d, as compared with 11.3 d for the most incompatible transplants. HLA-DR compatibility alone was associated with a mean survival time of 15.3 d, whereas HLA-DR-incompatible grafts had a mean survival time of 11.5 d. Incompatibilities for C3 proactivator, Glyoxalase I, and P did not have a significant effect upon graft survival. There was no evidence of an association between donor-recipient incompatibility at HLA-A, -B, or -C or at HLA-DR; such incompatibilities occurred independently of each other, in spite of the state of linkage disequilibrium known to exist between HLA-B and -DR. Incompatibilities for HLA-A, -B, and for HLA-DR exerted a potent additive effect upon graft survival. Skin grafts bearing one, two, or three incompatibilities had a mean survival time of 16.2, 13.7, and 10.7 d, respectively (P <0.0005).The results point to the important role played by the Ia-like products of the HLA complex (HLA-DR) in conditioning skin allograft survival in man. This consideration may be of direct relevance to the potential clinical usefulness of in vitro serological techniques for the detection of donor-recipient compatibility for HLA-DR.

Female↗