Ubiquitin-like polypeptide inhibits the proliferative response of T cells in vivo

The monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressi ve functions. Recently, we demonstrated that the recombinant form of the ub iquitin-like segment (rUbi-L) of MNSF beta, a 15.6 kDa-protein consisting o f a polypeptide with 36% homology with ubiquitin fused to the ribosomal pro tein S30, presented an antigen-nonspecific immunoregulatory action in a man ner similar to native MNSF Although this cytokine has been characterized in vitro, little is known about its effects in vivo. Thus, we investigated wh ether rUbi-L shows a suppressor activity in vivo. The proliferative respons e of Con A (5 mu g/ml)-stimulated splenocytes of mice treated with rUbi-L ( 500 ng/body) was notably decreased in a dose-dependent manner (max. 57 +/- 20%). In contrast, administration of high dose ubiquitin (50 mu g/body) sho wed a little, but significant, effect (30 +/- 7%). Interestingly, concomita nt addition of ubiquitin inhibited Ubi-L-induced suppression. Mice injected with rUbi-L without gelatin did not show any suppressive effect. NA4 (1 mu g/body), a neutralizing monoclonal antibody against rUbi-L, abolished the Ubi-L-mediated suppression. Therefore, ubiquitin-like polypeptide may be im plicated in the immune responses in vivo.