Peripheral blood mononuclear cells from autologous hematopoietic stem cell transplantation recipients produce and respond to IL-12.
Autologous hematopoietic stem cell transplantation effectively results in restoration of hematopoiesis, but induces an often prolonged period of T cell dysfunction including redistribution of T cell subsets and defective T cell proliferation. Because IL-2 production is markedly decreased following autologous stem cell engraftment, and because IL-12 has direct stimulatory effects on TH1 cells, a major source of IL-2, we investigated the production and responsiveness of IL-12 of peripheral blood mononuclear cells (PBMC) of autologous stem cell recipients in the first 6 months following engraftment. When stimulated with S. aureus Cowan I (SAC), PBMC from autologous hematopoietic transplant recipients in the early months following engraftment show no decrease in production of IL-12 as compared to control PBMC. Furthermore, transplant-derived PBMC appear to be functionally responsive to exogenously provided IL-12 as indicated by several criteria. In vitro proliferation of total PBMC and of isolated CD4+ T cells from transplanted recipients to PHA (1 microgram/ml) + IL-12 (20 U/ml) was comparable to controls, excluding the possibility that only NK or CD8+ cells respond to IL-12. Culture of both control and transplant-derived PBMC in PHA + IL-12 (20 U/ml) or IL-2 (100 U/ml) + IL-12 (20 U/ml) combinations yielded comparable production of IFN-gamma, one of the major biological effects of IL-12 in vivo, as well as equal production of TNF-alpha, a costimulatory factor of IL-12-mediated induction of IFN-gamma by NK cells. Taken together, this in vitro evidence suggests that following autologous transplantation, PBMC do not appear to have either decreased production of endogenous IL-12 or defective functional responsiveness to exogenously provided IL-12.
Guillaume
T
T
Laboratory of Experimental Oncology and Hematology, Catholic University of Louvain, Brussels, Belgium.
Kubin
M
M
Sekhavat
M
M
Rubinstein
D B
DB
Trinchieri
G
G
Symann
M
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12