Lymphokine-activated killer (LAK) cells. III. Characterization of LAK precursors and susceptible target cells within the murine thymus.
In our search for a biologic role for lymphokine-activated killers (LAK), we examined their generation from murine thymocytes. Normal adult thymocytes were capable of generating LAK upon culture with relatively large doses (500 to 1000 U/ml) of interleukin 2. Normal thymocytes were fractionated into four subsets by virtue of their co-expression of the Lyt-2 and L3T4 markers: Lyt-2+ L3T4+ (2+4+); 2+4-; 2-4+; and 2-4-. None of these subsets had any natural killer activity. Upon examining the ability of these subsets to generate LAK, it was found that the 2-4- subset was the most potent and required the smallest relative amounts of interleukin 2. In addition to lysing tumor cells, thymus-derived LAK were capable of killing "fresh" 2+4+ thymocytes. Fresh 2+4-, 2-4+, 2-4-, and cortisone-resistant thymocytes were resistant to lysis by LAK. Upon mitogen stimulation, however, the cortisone-resistant thymocytes and 2+4- thymocytes became LAK-susceptible. These data demonstrate a possible mechanism for the elimination of the 2+4+ thymocyte subset which is generally believed to be a "dead-end" population. Moreover, these data suggest a possible biologic role for LAK in the process of thymocyte maturation and intrathymic selection.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011994:Recombinant Proteins