摘要:

It has been suggested that deoxyspergualin, a new immunosuppressant, may be immunosuppressive via a purely antimonocyte action. As this appears to be unlikely, this study examines the effect of deoxyspergualin on lymphocyte and monocyte function in vivo and in vitro. It is demonstrated that deoxyspergualin inhibits human lymphocyte proliferation in response to mitogens and allogeneic stimulation. Furthermore, it is demonstrated that this inhibition occurs no matter whether the monocytes or lymphocytes are treated with the drug. The drug appears to have a more significant effect on the lymphocyte component; rhIL-2 appears partly to overcome the deoxyspergualin-induced inhibition of lymphocyte proliferation in response to allogeneic stimulation. In a rat renal transplant model, deoxyspergualin-treated animals demonstrated a moderate interstitial infiltrate in their transplant kidneys that comprised approximately 50% each of macrophages and lymphocytes. There was significantly less activation (e.g. IL-2R expression) in the treated kidney infiltrates compared to rejected controls. Thus deoxyspergualin is an agent with immunosuppressive effects on both lymphocytes and monocytes and would appear to have more marked effects on lymphocytes.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Treatment of stimulator cells with 0.1% paraformaldehyde for 60 sec or ultraviolet-B (UV-B) irradiation (1000 J/m) eliminates their ability to elicit T cell pro liferation in a primary mixed leukocyte reaction. How ever, a T cell response equal to 20–40% of control value could be elicited by paraformaldehyde fixed or UV-B irradiated cells providing the latter are incubated at 37°C for 18 hr prior to treatment. The incubation also induces a one-log increase in the density of fluorescence when the cells are stained with monoclonal antibodies against class II molecules DR and DP as well as the intercellular adhesion molecule —1 (ICAM-1). We inter pret this as an increase in the membrane expression of these structures following incubation. Chloroquine and cerulenin, known to inhibit protein degradation and antigen processing and presentation do not influence the upregulation in membrane expression of these class II and adhesion molecules, but do prevent incubation from overriding the effect of paraformaldehyde treatment. Colchicine, which reduces the traffic through tubular lysosomes, also has no effect on the upregulation but enhances allopresentation. We propose that incubation of stimulator cells in the presence of chloroquine and cerulenin results in the membrane expression of class II molecules without associated peptides. The inability of stimulator cells expressing such “nude” MHC molecules to elicit T cell proliferation after chemical modification could be due to easier crosslinking of the allodeterminants by paraformaldehyde when the binding site is empty but could also mean that nude MHC molecules are not per se immunogenic and become so only after acquisition of a peptide. It is also possible that chloroquine, NH4C1, and cerulenin block the expression of signals other than the class II and cell adhesion molecules that are essential for induction of T cell proliferation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present studies were undertaken to examine the ability of a viral pathogen to enhance immune alterations associated with parent → F1graft-versus-host re actions (GvHR) across defined donor/recipient MHC genetic disparities. Murine cytomegalovirus (MCMV) was administered concurrently with a parental lymphoid inoculum into unirradiated F1recipients in strain combinations limiting allogeneic differences to the entire MHC complex (class I/II), the H-2K region (class I), or H-2IA (class II) regions only. Alterations previously found to be associated with GvHR involving changes in the expression of Ly-6, Lyt-2, and L3T4 were examined to characterize the effects of MCMV. Mice receiving low numbers of class I/II-disparate parental cells or MCMV alone failed to exhibit significant GvHR-associated changes. In contrast, introduction of cells and virus resulted in marked alterations characteristic of F1recipients injected with a large parental cell inoculum alone. Concurrent virus and parental cells could also induce marked changes when administered across differences involving only a class I—disparate—but not class II—disparate only—P → F1combination. In addition to the phenotypic changes observed during the con current virus and class I GvHR, markedly reduced spleen cell proliferative activity and associated weight loss and mortality appeared to indicate that virus had enhanced this reaction. In total, these findings demonstrated that a donor/recipient class I MHC difference was necessary for virus and parental cells to induce the changes observed, and thus not all donor/recipient antigenic differences will result in a similar virus-induced effect. The results are discussed with respect to the potential mechanisms that may account for the apparent exacerbation of GvHR-associated alterations.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID