A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development.
A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.
Takahashi
I
I
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Kosaka
H
H
Oritani
K
K
Heath
W R
WR
Ishikawa
J
J
Okajima
Y
Y
Ogawa
M
M
Kawamoto
S
S
Yamada
M
M
Azukizawa
H
H
Itami
S
S
Yoshikawa
K
K
Tomiyama
Y
Y
Matsuzawa
Y
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000502:physiology* / Q000633:toxicity; D003602:Cytotoxicity, Immunologic; D004353:Drug Evaluation, Preclinical; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016853:Muromonab-CD3 / Q000494:pharmacology; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000276:immunology; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D016853:Muromonab-CD3; C410906:limitin; D016899:Interferon-beta; D010047:Ovalbumin