Effect of IL-2 in vitro on CTL generation in spleen cells of young and old mice: asialo GM1+ cells are required for the apparent restoration of the CTL response.
The role of asialo GM1+ (ASGM1+) cells and exogenous IL-2 in the age-related decline in allospecific CTL activity was evaluated. Primary CTL were generated in mixed leukocyte culture (MLC) [BALB/cANN (H-2d) anti C57BL/6N (H-2b)] and tested for allospecific lytic activity against the EL-4 (H-2b) cell culture line, and for non-MHC-restricted activity against WEHI-3 (H-2d) and YAC-1 (H-2a). Cultures included responder cell populations which had been treated with antibody to ASGM1 plus complement or complement alone, and irradiated stimulator cells, in the presence or absence of rIL-2 or crude IL-2-containing supernatants. The amount of rIL-2 used to accommodate the age-related decline in IL-2 production was determined empirically to be 500 U by assessing IL-2 production in MLCs containing responder cells from young versus old animals. rIL-2 appeared to restore the allospecific CTL activity generated by spleen cells of old mice to the level of that of young. However, treatment with anti-ASGM1 antibody revealed that this restoration was due to an effect of the IL-2 on ASGM1+ cells. The allospecific target cells, EL-4, were not sensitive to lymphokine-activated killer (LAK) cells induced by IL-2 alone under the conditions used. It is suggested that the apparent restoration was due to increased LAK-like (or MHC-nonrestricted) activity mediated by an ASGM1+ cell in the CTL precursor population.
Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, West Los Angeles, California 90073.
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Bloom
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Kubota
D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D006028:Glycosphingolipids; D007376:Interleukin-2; D007519:Isoantigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside