The superantigen-induced polarization of T cells in rat peripheral lymph nodes is influenced by genetic polymorphisms in the IL-4 and IL-6 gene clusters.
In recent years, it has become clear that the polarization of T cells depends on the genetic background. However, due to the complexity of the genetic background of each animal, a direct comparison of the phenotype is difficult. In this study, a new rat strain LEW.BN-4-10 carrying the chromosomal regions on chromosomes 4 and 10, which harbor IL-6 and IL-4 gene clusters of BN, has been bred on the genetic background of LEW. It was asked whether these two gene clusters influence the polarization of T cell responses. As a model, the Mycoplasma arthritidis mitogen (MAM)-induced inflammation was used focusing on the microenvironment of the draining lymph node (LN). The effect of differences in these regions was tested by comparing LEW.BN-4-10 and LEW rats under steady-state conditions and upon injection of MAM into the forepaw. Under steady-state conditions, the two strains showed differences in the dendritic cell (DC) subset composition. When MAM was injected, the number of T cells in LEW.BN-4-10 rats producing T(h)2 cytokines such as IL-4 and IL-13 was significantly increased compared with LEW. The data suggest that these differences in the microenvironments in LN of LEW and LEW.BN-4-10 rats resulted in different susceptibility to the disease (increase of cells in LN and paw swelling). In addition, deviations in the distribution and function of injected effector T cells were found in the LN of LEW and LEW.BN-4-10 rats after MAM treatment. The data indicate that the IL-6 and IL-4 gene clusters are involved in polarizing T cell responses in vivo.
Bode
Ulrike
U
Functional and Applied Anatomy, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. bode.ulrike@mh-hannover.de
Lörchner
Marc
M
Pabst
Reinhard
R
Wonigeit
Kurt
K
Overbeck
Silke
S
Rink
Lothar
L
Hundrieser
Joachim
J
D000818:Animals; D000942:Antigens, Bacterial; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000942:Antigens, Bacterial; D015850:Interleukin-6; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D018089:Superantigens; D015847:Interleukin-4