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A New IFN-Like Cytokine, Limitin Modulates the Immune Response Without Influencing Thymocyte Development¹

Isao Takahashi^*, Hiroshi Kosaka, Kenji Oritani^2,*, William R. Heath, Jun Ishikawa^*, Yu Okajima^*, Megumu Ogawa^*, Sin-ichiro Kawamoto^*, Masahide Yamada^*, Hiroaki Azukizawa, Satoshi Itami, Kunihiko Yoshikawa, Yoshiaki Tomiyama^* and Yuji Matsuzawa^*

Departments of ^* Internal Medicine and Molecular Science and Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan; and The Water and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia

A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN- 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– and -, 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- and -. 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.

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