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Defects of the common gamma chain subunit of the cytokine receptors (?c) or of Jak3, a tyrosine kinase required for ?c signal transduction, result in T-B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (>3,000/µL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+HLA-DR+ CD62Llo), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in ?c-/y and in Jak3-/-mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.

1. Evidence is presented which indicates that pulmonary megakaryocytes do not originate in the lungs but elsewhere in the body and are carried to the lungs in the venous blood. 2. Some megakaryocytes in the lungs evidently deliver platelets to the blood. 3. Surgery is a potent stimulus to megakaryocyte production; the numbers of megakaryocytes found in the lung postoperatively is significantly increased.

1. Megakaryocytes were demonstrated in central venous blood of each of 23 patients who underwent cardiac catheterization. Cell counts ranged from 0.7 to 5.9 megakaryocytes per ml. of blood; the equivalent of one-third of these cells were considered to contain a full complement of cytoplasm. It has become evident that megakaryocytes are normal constituents of blood. 2. In an attempt to quantify megakaryocyte migration from the bone marrow it was calculated that from 20-50 per cent of the mature megakaryocyte population enters the blood and ultimately reaches the lungs. The possibility that all megakaryocytes migrate from the marrow is not precluded with certainty by these studies. 3. It was estimated that from 7-17 per cent of the body’s platelets are released in the pulmonary capillaries. If all megakaryocytes migrate from the bone marrow, then as much as 33 per cent of the platelet population is delivered to the blood in the lungs.