A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT1O. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4+, OKT5+, OKT6+ "common" thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4+ and OKT5+ subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3+) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.The importance of a thymic microenvironment in the differentiation and functional maturation of T cells has been demonstrated in several species. Moreover, profound changes in cell-surface antigens mark the various stages of T-cell ontogeny (1-7). For (12). These thymcytes were the most functionally mature and probably ready for peripheral exportation. Human peripheral T cells also consist of functionally distinct subsets (13)(14)(15)(16)(17)(18)(19).In the present study, we used a series of monoclonal antibodies reactive selectively with subpopulations of human thymocytes and inducer and suppressor T-cell subsets in order to further define stages of thymic differentiation (18, 19). We show that three major stages of intrathymic differentiation exist and that the majority of tumor populations from patients with acute lymphoblastic leukemia of T-cell lineage (T-ALL) can be shown to

Antilymphocytic serum (ALS) is the name given to an antiserum raised in members of one species by the injection of lymphocytes or lymphoid cells taken from members of another species. It has the power not merely to prevent or delay the onset of immunological reactions leading to the rejection of homografts,1' 2 but also to arrest reactions already in progress.2' 3 This combination of properties is unique, and since ALS is devoid of acute toxicity, and is indeed, in transplantation systems, the most powerful immunosuppressive agent yet described, its clinical and experimental potentialities are worth close attention.The experiments reported here are intended to throw further light on the nature and mode of action of ALS.Materials and Methods.-Preparation of antiserum: Antisera were raised by giving New Zealand rabbits two successive intravenous injections 14 days apart of a single-celled suspension of 109 living thymocytes from young female CBA mice. The rabbits were bled 7 days after the second injection, and the serum was heated to 56°for 30 min, filtered, and stored at -20°. This simple regimen served also for lymphocyte fractions and for cells other than lymphocytes, and the antisera so prepared required no absorption with red cells. Longer courses of injection usually yielded less effective antisera, perhaps because of a change in the physical character of the operative antibodies, or because of interference by antibodies to minor or irrelevant constituents of the immunizing cells. Antisera were always injected by the subcutaneous (subintegumentary) route.Assay; Skin grafting: The strength of a sample of ALS was measured in terms of its power to prolong the life of A-strain tail skin homografts on adult male CBA mice. In a typical experiment, each member of a uniform panel of mice received 0.5 ml ALS on the second and again on the fifth day after grafting (i.e., on days +2 and +5 in the now widely used notation). The results are figured as survival curves showing, day by day, the number of mice still bearing surviving grafts, and are expressed numerically either as the mean expectation of life (MEL) of a graft at grafting, or as the median survival time (MST). The error function cited is the standard deviation (SD). The MEL of A-strain tail skin homografts on adult CBA males is 11.6 ± 1.3 days SD (MST 11.5 days).3Abrogation of the Second-Set Response. The sensitivity aroused in CBA mice by grafts of A skin, as measured by the survival time of a second graft transplanted at various intervals after the rejection of a first, is still clearly in force after 35 weeks.4 For the first 10 weeks after the rejection of first-set grafts, the MST of second-set grafts does not exceed 6 days. We have already shown3 that under the protection afforded by 4 X 0.5 ml ALS given on days -1, +1, +3, +5, the MST of second-set grafts exceeded 40 days (maximum 210 days). However, when 11 days was allowed to pass between the completion of such a course of injections and the transplantation of second-set grafts, the MST fell to betwee...

The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June 1984 to better define the characteristics of typhlitis and its optimum management. Twenty-five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad-spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra-abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.