Enhanced Th2-like responses in IL-1 type 1 receptor-deficient mice.
IL-1 has a number of effects on T cell growth but a specific role for IL-1 in T cell responses in vivo has not been elucidated. In this study the role of IL-1 in Th1/Th2 responses was examined in mice deficient for the IL-1 type 1 receptor (IL-1RI-/-) during cutaneous Leishmania major infection or following immunization with keyhole limpet hemocyanin (KLH). After inoculation of L. major stationary phase promastigotes into the hind footpad, both IL-1RI-/- and wild-type (WT) mice developed small lesions which resolved spontaneously. Lymph node cells from infected IL-1RI-/- mice produced significantly more IL-4 and IL-10 than those from WT mice following antigenic stimulation in vitro. Splenocytes from IL-1RI-/- and WT mice showed similar levels of antigen-induced proliferation. In contrast, splenocyte cultures from the IL-1RI-/- mice contained significantly more IL-4 than those from WT mice. Similar results were also obtained after immunization with KLH. While lymph node cells from both IL-1RI-/- and WT mice displayed similar levels of KLH-specific proliferation, those from IL-1RI-/- mice produced significantly more IL-4 than those from WT mice. Conversely, antigen-stimulated lymph node cells from WT mice secreted significantly greater amounts of IFN-gamma as compared with those from IL-1RI-/- mice. These data indicate that while IL-1 is not required for mounting an immune response or antigen-dependent proliferation, it appears to be required for normal regulation of Th1/Th2 responses and may function to negatively regulate IL-4 expression.
Satoskar
A R
AR
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston 02115, USA. asatoska@hsph.harvard.edu
Okano
M
M
Connaughton
S
S
Raisanen-Sokolwski
A
A
David
J R
JR
Labow
M
M
D000818:Animals; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D008088:Listeriosis / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*
D017472:Receptors, Interleukin-1; D015847:Interleukin-4; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin