LYMPHOKINE SYNTHESIS INVIVO IN AN ACUTE MURINE GRAFT-VERSUS-HOST REACTION - MESSENGER-RNA AND PROTEIN MEASUREMENTS INVIVO AND INVITRO REVEAL MARKED DIFFERENCES BETWEEN ACTUAL AND POTENTIAL LYMPHOKINE PRODUCTION LEVELS
- Author(s)
- TROUTT, AB; Kelso, A;
- Details
- Publication Year 1993-04,Volume 5,Issue #4,Page 399-407
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- The in vivo activation of lymphokine-producing cells was analyzed in the first 7 days of an acute graft-versus-host reaction (GVHR) induced by injection of C57BL/6 spleen cells into irradiated DBA/2 mice. Although the GVHR was accompanied by a 1000-fold increase in serum IL-6 titers, circulating levels of other lymphokines were low (IL-3, IFN-gamma, and GM-CSF) or undetectable (IL-2 and IL-4). Spleen and lymph node cells from these mice nevertheless produced elevated levels of IL-3, IFN-gamma, GM-CSF, and IL-6 when cultured for 24 h without stimulation; culture with anti-CD3 antibody further increased IL-2, IL-3, IL-4, IFN-gamma, and GM-CSF production by at least 20-fold. Both constitutive and anti-CD3-induced synthesis of all the lymphokines was mediated by CD3+ cells. Messenger RNA analyses revealed the presence of IL-6, IFN-gamma, and GM-CSF transcripts in freshly harvested GVHR spleen cells and increased expression of IL-2, IL-3, IL-4, IFN-gamma, and GM-CSF mRNAs following anti-CD3 stimulation in vitro. In vivo, however, IL-3 mRNA was barely detectable even following cDNA amplification by polymerase chain reaction. In vivo restimulation of day 5 GVHR mice by injection of concanavalin A enhanced expression of IL-3, IL-6, IFN-gamma, and GM-CSF mRNAs and markedly increased serum titers of the corresponding lymphokines, which peaked 6 - 12 h after injection at levels at least 10- to 100-fold higher than in concanavalin A-treated normal mice. It is concluded that the GVHR induces only modest or negligible rises in systemic levels of some lymphokines (IL-2, IL-3, IL-4, IFN-gamma, and GM-CSF) and marked rises in others (IL-6). The responses of GVHR cells to restimulation in vivo or in vitro indicate, however, that the reaction primes lymphoid cells for high-level synthesis of all these lymphokines.
- Publisher
- OXFORD UNIV PRESS UNITED KINGDOM
- Keywords
- COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL CEREBRAL MALARIA; CD8+ T-CELLS; ANTICYTOKINE ANTIBODIES; MONOCLONAL-ANTIBODY; GROWTH-FACTOR; SERUM LEVELS; MULTI-CSF; IFN-GAMMA
- Publisher's Version
- https://doi.org/10.1093/intimm/5.4.399
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1993-04-01 12:00:00