Activity of human placental gamma globulin in blocking immune functions in vitro and in abrogating the xenogeneic, local graft-versus-host reaction.
In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), we have examined the effect of PGG in vitro and in a model of the xenogeneic, local graft-versus-host reaction (LGVHR). PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P less than 0.005) and depressed interleukin-2 (IL-2) levels in such cultures at 72 hours (P less than 0.01). In contrast phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced T and B lymphocyte blastogenesis was not affected by such PGG treatment. PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability. Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation. An immunosuppressive effect of PGG on the LGVHR was tested in a model of intracutaneous transplantation of PGG-treated human lymphocytes into cyclophosphamide-immunosuppressed rats. Lymphoprep-separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing: (1)PGG, 4 mg/ml, (2) human plasma albumin, 4 mg/ml, (3) mitomycin-C, 25 micrograms/ml, or (4) no additive. Cells of each preparation (3 X 10(7) cells in 0.1 ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells, each rat received [125I]UdR (10 muCi) intraperitoneally and was killed after 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhong
R K
RK
Dong
Y H
YH
Lu
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DP
D000818:Animals; D002455:Cell Division; D006087:Graft vs Host Reaction; D007166:Immunosuppressive Agents; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D010920:Placenta / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D005719:gamma-Globulins / Q000276:immunology* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D005719:gamma-Globulins