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Lymphokines and monokines
621
Abstracts
EFFECTS OF THYMOSTIMULIN
(TS) ON INTERFERON
(IFN) AND INTERLEUKIN-2
(IL-2) PRODUCTION
A.M.Liberati, P.Andreani, AoPecci, M.G.Proietti, R.Sbarretti and A.Puxeddu Clinica Medica (N), UniversitA di Peruoia, Ospedale Civile di Terni~ Terni,
9O
Italia.
Previous experiments on HD patients in CR,but with persistent cellular immunity de leers,showed that TS improved o r fully restored the percentages ofcirculating ENR+~ T5 + and T~ + cells and enhanced NK cell activity (A.M.Liberati et al.,Cancer Immunol. Immunoter.,in press). A second s t u d y t e s t e d whether changes in T cell subset propor_ tions were associated with modifications in vitro IL-2 and IFN-y production and in vivo type I IFN serum levels. Preliminary results indicate increased IL-2 a n d IFN-y synthesis in more than 50% o f patients tested,but no changes in type I IFN production. Improved IL-2 and IFN-y levels a r e s e e n in p t s with initial low levels of these im mane mediators. In c o n t r a s t t h e r e is n o i m p r o v e m e n t and in s o m e c a s e s a decrease i~ IL-~ and IFN-~ synthesis in pts with initial normal or hioh levels. Therefore TS in d u c e d T cell d i f f e r e n t i a t i o n a n d m a t u r a t i o n is associated with increased IL-Z and IFN-~ production.
WEDNESDAY 8 MAY LYMPHOKINES
AND MONOKINES
NON-CYTOTOXIC FUNCTIONS OF HIrMAN LARGE GRANULAR LYMPHOCYTES (LGL) G.Scala, P.Allavena*, J.R.Ortaldo***, J.Y.Djeu **~*, R.B.Herberman*** and J.J.Oppenheim**. Institute of Biochemical Sciences, Naples; Institute "M. Negri"*,Milan; LMI**and BTB***,NCI-FCRF, Frederick, MU 21701; FDA****,Bethesda, MD 21201. We report in this study that human LGL in response to appropriate stimuli produce a variety of cytokines, including interleukin-i (IL-I), interleukin-2 (IL-2) and interferon( I F N - ) . ~L-I was .main~ produ%efl_ in response to E. coli Lipopolysaccharide (LPS) by LGL with OKMI , B73.1 ±, DR , OKTII -- phenotype. IL-2 was secreted in response to phitoe~oagg~tinin ( P ~ ) and to+natural killer (NK) sensitive targets (K562) by LGL with OKMI , D R ' - , B73.1 '-, OKTII-- surface phenotype. The close association of surface markers such as OKMI or B73.1 with NK activity of LGL, suggests that some LGL may exert both NK function and secretion of cytokines. This possibility was confirmed when clones of LGL with NK activity, expanded in IL-2 supplemented medium, were tested for secretion of IL-I, IL-2 or IFN- . Since the cytokines mediate a variety of immunological functions, the results suggest that LGL may play a major role in immunoregulat~on. Sn line ~ t h this possibility, we present data showing that subset(s) of LGL OKMI-, DR , OKTII J- can exert an effective accessory cell function for T lymphocyte proliferative response to soluble stimulants S. aureus protein A (SPA) or streptolysin-O (SLO) and can stimulate an autologous or allogeneic mixed leukocyte reaction.
27
HUMAN INTERLEUKIN-I (ILl) STIMULATES THE G R O ~ H OF ROHA-9, AN EBV-TRANSFORMED HUMAN B CELL LINE. G. Scala,G. Morrone, A. Visconti. Institute of Biochemical Sciences, II Medical School, 80131 Naples,Italy. Recently an human EBV-B cell line, ROHA-9, has been reported to secrete an ILl-like factor (Scala et al. J. Exp. Med.159,1637,1984). Since further studies suggested that this ILl-like factor stimulated the growth of ROHA-9 cells, we tested whether human monocyte-derived ILl migth exert a similar growth-promoting activity. Partially purified human ILl from E.coli lipopolysaccharide (LPS) or silica-stimulated monocytes, free of any known biological activities, stimulated the growth of ROHA-9 cells in a dose-dependent way, while other non ILl-producing EBV-B cell lines were unresponsive to ILl. Human recombinant interleukin-2, human recombinant Interferon(IFN)-a and y an~ purified IFN-8, were ineffective when tested at concentrations up to 2 . 5 and 5x10units/ml for IL2 or IFN preparation respectevely. Furthermore B cell Growth Factor (BCGF)-containing supernatants and murine ILl from LPS-stimulated P388D1 cell line, both were negative in such ROHA-9 proliferation assay. From limiting dilution in methyl-cellulose semisolid medium supplemented with ILl a subclone, ROHA-gHC3, was isolated which was particularly sensitive to the growth-promoting activity of ILl. The results suggest that human ILl, in addition to its actions in immunoregulation and inflammation, plays the role of growth factor for ROHA-9 cells and perhaps for othe ILl-producing neoplastic cells.
28
Abstracts
EFFECTS OF THYMOSTIMULIN
(TS) ON INTERFERON
(IFN) AND INTERLEUKIN-2
(IL-2) PRODUCTION
A.M.Liberati, P.Andreani, AoPecci, M.G.Proietti, R.Sbarretti and A.Puxeddu Clinica Medica (N), UniversitA di Peruoia, Ospedale Civile di Terni~ Terni,
9O
Italia.
Previous experiments on HD patients in CR,but with persistent cellular immunity de leers,showed that TS improved o r fully restored the percentages ofcirculating ENR+~ T5 + and T~ + cells and enhanced NK cell activity (A.M.Liberati et al.,Cancer Immunol. Immunoter.,in press). A second s t u d y t e s t e d whether changes in T cell subset propor_ tions were associated with modifications in vitro IL-2 and IFN-y production and in vivo type I IFN serum levels. Preliminary results indicate increased IL-2 a n d IFN-y synthesis in more than 50% o f patients tested,but no changes in type I IFN production. Improved IL-2 and IFN-y levels a r e s e e n in p t s with initial low levels of these im mane mediators. In c o n t r a s t t h e r e is n o i m p r o v e m e n t and in s o m e c a s e s a decrease i~ IL-~ and IFN-~ synthesis in pts with initial normal or hioh levels. Therefore TS in d u c e d T cell d i f f e r e n t i a t i o n a n d m a t u r a t i o n is associated with increased IL-Z and IFN-~ production.
WEDNESDAY 8 MAY LYMPHOKINES
AND MONOKINES
NON-CYTOTOXIC FUNCTIONS OF HIrMAN LARGE GRANULAR LYMPHOCYTES (LGL) G.Scala, P.Allavena*, J.R.Ortaldo***, J.Y.Djeu **~*, R.B.Herberman*** and J.J.Oppenheim**. Institute of Biochemical Sciences, Naples; Institute "M. Negri"*,Milan; LMI**and BTB***,NCI-FCRF, Frederick, MU 21701; FDA****,Bethesda, MD 21201. We report in this study that human LGL in response to appropriate stimuli produce a variety of cytokines, including interleukin-i (IL-I), interleukin-2 (IL-2) and interferon( I F N - ) . ~L-I was .main~ produ%efl_ in response to E. coli Lipopolysaccharide (LPS) by LGL with OKMI , B73.1 ±, DR , OKTII -- phenotype. IL-2 was secreted in response to phitoe~oagg~tinin ( P ~ ) and to+natural killer (NK) sensitive targets (K562) by LGL with OKMI , D R ' - , B73.1 '-, OKTII-- surface phenotype. The close association of surface markers such as OKMI or B73.1 with NK activity of LGL, suggests that some LGL may exert both NK function and secretion of cytokines. This possibility was confirmed when clones of LGL with NK activity, expanded in IL-2 supplemented medium, were tested for secretion of IL-I, IL-2 or IFN- . Since the cytokines mediate a variety of immunological functions, the results suggest that LGL may play a major role in immunoregulat~on. Sn line ~ t h this possibility, we present data showing that subset(s) of LGL OKMI-, DR , OKTII J- can exert an effective accessory cell function for T lymphocyte proliferative response to soluble stimulants S. aureus protein A (SPA) or streptolysin-O (SLO) and can stimulate an autologous or allogeneic mixed leukocyte reaction.
27
HUMAN INTERLEUKIN-I (ILl) STIMULATES THE G R O ~ H OF ROHA-9, AN EBV-TRANSFORMED HUMAN B CELL LINE. G. Scala,G. Morrone, A. Visconti. Institute of Biochemical Sciences, II Medical School, 80131 Naples,Italy. Recently an human EBV-B cell line, ROHA-9, has been reported to secrete an ILl-like factor (Scala et al. J. Exp. Med.159,1637,1984). Since further studies suggested that this ILl-like factor stimulated the growth of ROHA-9 cells, we tested whether human monocyte-derived ILl migth exert a similar growth-promoting activity. Partially purified human ILl from E.coli lipopolysaccharide (LPS) or silica-stimulated monocytes, free of any known biological activities, stimulated the growth of ROHA-9 cells in a dose-dependent way, while other non ILl-producing EBV-B cell lines were unresponsive to ILl. Human recombinant interleukin-2, human recombinant Interferon(IFN)-a and y an~ purified IFN-8, were ineffective when tested at concentrations up to 2 . 5 and 5x10units/ml for IL2 or IFN preparation respectevely. Furthermore B cell Growth Factor (BCGF)-containing supernatants and murine ILl from LPS-stimulated P388D1 cell line, both were negative in such ROHA-9 proliferation assay. From limiting dilution in methyl-cellulose semisolid medium supplemented with ILl a subclone, ROHA-gHC3, was isolated which was particularly sensitive to the growth-promoting activity of ILl. The results suggest that human ILl, in addition to its actions in immunoregulation and inflammation, plays the role of growth factor for ROHA-9 cells and perhaps for othe ILl-producing neoplastic cells.
28