T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection with Nippostrongylus brasiliensis.
The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is critical for development of normal Th2-type responses. To elucidate the role of T1 in vivo, we generated T1-deficient mice and a T1-transgenic strain which secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the Th2 immune response induced by infection with the parasitic nematode Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node cells was similar in all groups of N. brasiliensis-infected mice, a decrease in IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc-transgenic mice compared to control littermates. This difference in IL-5 production did not influence blood eosinophilia, but recruitment of eosinophils into lung tissue, especially in T1-Fc-transgenic mice was slightly decreased. However, induction of all other immune parameters was normal and both T1-deficient and T1-Fc-transgenic mice were able to clear the parasite infection within 12 days with kinetics similar to those in control mice. Therefore, in contrast to previous suggestions, we conclude that the T1 protein is not obligatory for normal development of Th2 immune responses.
Department of Pathology, University Hospital Zürich, Switzerland.
K A
KA
Senn
K D
KD
McCoy
K J
KJ
Maloy
G
G
Stark
E
E
Fröhli
T
T
Rülicke
R
R
Klemenz
D000818:Animals; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015848:Interleukin-5 / Q000096:biosynthesis; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C079241:IL1RL1 protein, human; C486189:Il1rl1 protein, mouse; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015848:Interleukin-5; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E