In vitro T cell unresponsiveness following low-dose injection of anti-CD3 MoAb

Anti-CD3 MoAb treatment is widely used as an immunosuppressive therapy. In the present study we examined the in vitro T cell response in mice having received 24 h before a single i.v. injection of 10 μg of anti-CD3 MoAb. We found that splenocytes from these mice displayed a dramatically decreased proliferative response to the T cell mitogens concanavalin A (Con A), anti-CD3, phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) + calcium ionophore, while the effect of lipopolysaccharide (LPS) was not impaired. T cell suppression persisted for about 10 days after anti-CD3 injection, returning to normal within 15 days. The F(ab')₂ fragment of anti-CD3 had no such effect, indicating the requirement for in vivo activation. At the dose used, anti-CD3 resulted neither in T cell depletion nor in down-modulation of the CD3/T cell receptor (TCR) complex. The low proliferation was also not explained by apoptosis, following secondary challenge with Con A. Splenocytes from anti-CD3-injected mice were highly responsive to IL-2, but generated little or no IL-2, IL-3, IL-4 and interferon-gamma (IFN-γ) when exposed to Con A. Normal cytokine production could not be restored by the addition of optimal doses of IL-2 during Con A stimulation. Transforming growth factor-beta (TGF-β) was the only cytokine whose mRNA expression was not modified in stimulated splenocytes from anti-CD3-injected mice. Furthermore, anti-TGF-β antibodies increased Con A-induced T cell proliferation, but not cytokine production.     

Human marrow stromal cells: response to interleukin-6 (IL-6) and control of IL-6 expression

Production of interleukin-6 (IL-6) by marrow stromal cells from human long-term marrow cultures and from stromal cells transformed with simian virus 40 was examined. As with other cultured mesenchymal cells, unstimulated stromal cells produced undetectable amounts of IL-6 mRNA when assayed by Northern blots. However, within 30 minutes after exposure of transformed marrow stromal cells to the inflammatory mediators, recombinant human interleukin-1 alpha (IL-1 alpha) or recombinant human tumor necrosis factor alpha (TNF alpha), significant increases in IL-6 expression were observed. The time course of IL-6 mRNA upregulation in transformed marrow stromal cells with IL-1 alpha and TNF alpha differed: The maximal response to TNF alpha was observed at 30 minutes whereas that to IL-1 alpha occurred at 8 hours. Although IL-6 at a concentration of 500 U/mL was inhibitory to adherent transformed marrow stromal cell proliferation, a concentration- dependent stimulation of anchorage-independent colony growth was observed when the cells were plated in semisolid medium with IL-6. The stromal cell colony-stimulating effect of IL-6 was abrogated by a neutralizing antibody to IL-6. Moreover, the heteroserum with anti-IL-6 activity and two anti-IL-6 monoclonal antibodies partially blocked autonomous and IL-1 alpha-induced colony formation, suggesting that colony formation by transformed marrow stromal cells may require IL-6. Clonal-transformed stromal cell lines were derived from the anchorage- independent stromal cell colonies. Both IL-6 mRNA and protein were constitutively produced at high levels. The addition of IL-6 to either long-term marrow culture adherent cells or transformed marrow stromal cells downregulated the expression of collagen I, a major stromal cell matrix protein. Thus, IL-6 affects proliferation of stromal cells and influences their production of extracellular matrix, suggesting that IL- 6 may have indirect as well as direct influences on hematopoietic cell proliferation.     

重视肺炎支原体的耐药问题

肺炎支原体(Mycoplasma Pneumoniae)是社区获得性肺炎(Community-Acquired Pneumonia,CAP)的常见致病原.一项全球性CAP病原学调查结果显示,肺炎支原体肺炎占CAP的12%,在所有非典型病原体所致的CAP中超过50%[1].     

Gestational trophoblastic tumor in pregnancy: a case report and review of the literature

A case of gestational trophoblastic tumor (GTT) concurrent with an intrauterine pregnancy is reported in a 21-year-old gravida 2 para 0 (0010) who presented with dyspnea, orthopnea, headache, and blurring of vision at 33 weeks age of gestation. She had a history of hydatidiform mole for which curettage was done. Chest radiograph showed pulmonary metastases, with pleural effusion on both lungs. Serum beta subunit of human chorionic gonadotropin was abnormally elevated for age of gestation. Due to worsening maternal pulmonary condition, the patient underwent primary, low segment cesarean section and was subsequently started on multidrug chemotherapy. This is the first reported case of GTT in pregnancy in the Philippines in which both the mother and the infant survived. Several hypotheses regarding its origin, its diagnosis, and its management and prognosis are presented. This case report emphasizes the importance of early diagnosis and treatment to improve the prognosis of both the mother and the infant.