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Donor’s and recipient’s antigen presenting cells cooperatively enhance the allo-reactive proliferation of peripheral blood lymphocytes.
Antigen-presenting cells (APC) play important roles in the allo-reactive proliferation of T cells in vitro and in the allo-graft rejection in vivo. This work was aimed at establishing whether a co-operation of any kind occurs between donor's and recipient's APC during allo-reactions, and whether certain cell surface molecules, such as beta 2-microglobulin (beta 2m) and human leucocyte antigens (HLA), are involved in such an interaction. The data herein reported show that the allo-reactive proliferation of peripheral blood lymphocytes (PBL) is markedly intensified by a positive co-operation between donor's and recipient's APC. Such a synergistic co-stimulatory action can be significantly hindered by a monoclonal antibody aimed against beta 2m while being not changed by monoclonal antibodies binding to either HLA-A-B-C or HLA-DR molecules. Hence, our preliminary results indicate that a positive interaction between donor's and recipient's APC may be of importance for allo-graft rejection
The preferential homing of lymphocytes into the epidermis causes the inertia of dermis in allo-skin immune rejection
The preferential homing of lymphocytes into the epidermis causes the inertia of dermis in allo-skin immune rejectio
A beta2-microglobulin-dependent mechanism enhances the DNA-synthetic response of recipient’s lymphocytes to the donor’s cells
A beta2-microglobulin-dependent mechanism enhances the DNA-synthetic response of recipient’s lymphocytes to the donor’s cell
ß2-microglobulin-dipendent positive co-operation between antigen-presenting cells
ß2-microglobulin-dipendent positive co-operation between antigen-presenting cell
Il parathormone-related peptide (PTH-rP) modula la attività proliferativa dei cheratinociti di Uomo adulto coltivati su supporti polietilenici in medium sintetico MCDB 153.
Il parathormone-related peptide (PTH-rP) modula la attività proliferativa dei cheratinociti di Uomo adulto coltivati su supporti polietilenici in medium sintetico MCDB 153
An investigation into the mechanisms by which the human dermis does not significantly partake to the rejection of allo-skin grafts.
The dermis is an important element in skin substitutes and in allo- or xeno-skin grafts. However, the reason(s) why dermis does not significantly induce the immune rejection reaction in vivo remain(s) hitherto unknown. To clarify the mechanisms underlying this phenomenon, we undertook the evaluation of: (i) the response of the peripheral blood mononuclear cells (PBM) to isolated allo-dermal cells or to pieces of or to whole allo-dermis, (ii) the migration and homing of the PBM inside allo-dermis or split thickness allo-skin, (iii) the distribution of the ICAM-1 protein within skin, and (iv) the features expressed by the PBM that migrate into allo-skin. The results herein presented show that (1) the isolated allo-dermal cells had the highest and the whole allo-dermis the lowest capacity to initiate the reactive proliferation of the PBM in vitro; (2) in an allo-skin/PBM co-culture model, most of the PBM slowly, yet preferentially, migrated to and homed inside the allo-epidermal compartment, instead of staying in the allo-dermis; (3) under the conditions employed, rather little ICAM-1 could be immunohistochemically detected within the epidermis, conversely, both the dermal cells and the dermal matrix were ICAM-1 positive; and (4) most of the PBM migrating into the allo-skin pieces expressed either the CD18 or the CD19 or the CD8 molecule, yet very few of them exhibited the LFA-1-antigen, and none of them were found to be CD4 positive.2+Therefore, we conclude that becaus
PTH1-34 modulates the proliferation of adult human keratinocytes cultured in MCDB 153 synthetic medium
PTH1-34 modulates the proliferation of adult human keratinocytes cultured in MCDB 153 synthetic mediu
An anti-beta2-microglobulin monoclonal antibody prevents the reactive proliferation of lymphocytes elicited by allo-human epidermal cells.
An anti-beta2-microglobulin monoclonal antibody prevents the reactive proliferation of lymphocytes elicited by allo-human epidermal cells. The same antibody does not affect the proliferation of the keratinocyte
Prolongation of survival of alloskin grafts with no concurrent general suppression of the burned patient's immune system: A preliminary clinical investigation
The adequate management of burns is the requisite to save the patient's life, to prevent the onset of secondary infections and to obtain healing with acceptable cosmetic results. Previous data have shown that the use of alloskin grafts in the acute phase of burns yields the best clinical results. Unfortunately, this approach is curbed by the patient's immune response which induces the rejection of the allografts. In this report we endeavoured to solve this problem by ways that would not imply the general suppression of the patient's immune system. Thus, we can now report that a longer survival of alloskin grafts can be induced in situ by pretreating the alloskin samples to be grafted with both an anti-beta-2-microglobulin monoclonal antibody (beta-2mAb) and irradiation with ultraviolet-C light (UVC). The advantage of our novel approach is that it does not need any concomitant administration of immunosuppressive agent(s) to the burned patients. In this study, we followed five severely burned patients grafted with alloskin samples pretreated with either beta-2mAb or beta-2mAb plus UVC irradiation. In comparison with untreated alloskin samples from the same source grafted in parallel, the mean survival time (MST) of the beta-2mAb-pretreated alloskin specimens increased by 35 per cent (i.e. from 18.3 +- 3.2 days to 24.7 +- 5.5 days) in three patients. Moreover, the MST of the alloskin grafts pretreated with both beta-2mAb and UVC irradiation was lengthened by 100 per cent (i.e. from 18.5 +- 4.5 days to 37.0 +- 8.0 days) in the remaining two patients. These preliminary results lend credence to the view that local immune suppression could be achieved in situ by our approach via; (1) the impairment of the proper functions of the HLA-class I antigen by the bound beta-2mAb; and (2) the inhibition of immune reactions taking place inside the alloskin grafts by some immunosuppressive signal(s) generated by the UVC-pretreated alloepidermal cells. Hence, our approach stands as an exciting and useful alternative to the otherwise well-known, deleterious general suppression of the burned patient's immune system
A novel approach to extend the survival of skin xenografts without entailing general immunosuppression or systemic toxicity
The feasibility of using antigenically disguised skin xenotransplants to cover extensive burns for a suitable time lag without administering immunosuppressive drugs was tested experimentally. Pieces of human skin that had been preincubated for 3 h at 37 degrees C with either mouse anti-human beta 2-microglobulin monoclonal antibody (beta 2m-McAb) or PBS (controls) were grafted onto the backs of immunologically competent Swiss mice, and the time required for their rejection or substitution by normal autogenous skin was determined. Thus, it was found that the beta 2m-McAb-pretreated xenografts had a significantly longer mean survival time than the control grafts. An even longer skin xenograft MST was obtained when beta 2m-McAb was repeatedly injected, at weekly intervals, just beneath the transplants. Parallel immunohistochemical studies showed that the beta 2m-McAb entered the grafts and was bound to its targets both in epidermis and dermis. Moreover, a small amount of beta 2m-McAb administered at the outset significantly hindered the reactive proliferation of primed mouse spleen cells cultured in the presence of human epidermal cells. Finally, neither toxic effects nor a weakening of immune competence were elicited by repeated intraperitoneal injections of beta 2m-McAb. Therefore, it seems expedient to propose the use of beta 2m-McAb to delay the rejection of skin xenografts as this antibody harmlessly prevents, wholly or in part, the activation of the recipients' lymphocytes. This would positively aid any patient urgently needing xenograft cover of extensive burns
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