Cellular immunity function in HIV-1-infected persons

The data on the state of cell-mediated immunity in patients with AIDS-related complex are presented. The synthetic peptide of membrane protein gp120 of HIV-1 was shown to inhibit leukocyte adhesion in persons under examination, as well as to have the tendency towards inhibiting the chemotaxis of migratory cells. The maximum effect was achieved at a peptide concentration of 10(-6) M. The data obtained in this investigation suggest the presence of specific cell-mediated sensitization to the fragment of protein gp120, detected by the adhesion inhibition test with the use of spectrophotometric techniques and the capillary evaluation of the chemotaxis of migrating cells, in patients with AIDS-related complex.     

Reduction of human T-cell leukemia virus type 1 (HTLV-1) proviral loads in rats orally infected with HTLV-1 by reimmunization with HTLV-1-infected cells

Human T-cell leukemia virus type 1 (HTLV-1) persistently infects humans, and the proviral loads that persist in vivo vary widely among individuals. Elevation in the proviral load is associated with serious HTLV-1-mediated diseases, such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, it remains controversial whether HTLV-1-specific T-cell immunity can control HTLV-1 in vivo. We previously reported that orally HTLV-1-infected rats showed insufficient HTLV-1-specific T-cell immunity that coincided with elevated levels of the HTLV-1 proviral load. In the present study, we found that individual HTLV-1 proviral loads established in low-responding hosts could be reduced by the restoration of HTLV-1-specific T-cell responses. Despite the T-cell unresponsiveness for HTLV-1 in orally infected rats, an allogeneic mixed lymphocyte reaction in the splenocytes and a contact hypersensitivity response in the skin of these rats were comparable with those of naive rats. HTLV-1-specific T-cell response in orally HTLV-1-infected rats could be restored by subcutaneous reimmunization with mitomycin C (MMC)-treated syngeneic HTLV-1-transformed cells. The reimmunized rats exhibited lower proviral loads than untreated orally infected rats. We also confirmed that the proviral loads in orally infected rats decreased after reimmunization in the same hosts. Similar T-cell immune conversion could be reproduced in orally HTLV-1-infected rats by subcutaneous inoculation with MMC-treated primary T cells from syngeneic orally HTLV-1-infected rats. The present results indicate that, although HTLV-1-specific T-cell unresponsiveness is an underlying risk factor for the propagation of HTLV-1-infected cells in vivo, the risk may potentially be reduced by reimmunization, for which autologous HTLV-1-infected cells are a candidate immunogen.     

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.     

Justice, HMOs, and the invisible rationing of health care resources

Fleck divides his paper on health care rationing into three parts. In the first part, he presents and critically assesses the moral problems posed by invisible rationing mechanisms. He claims that such mechanisms, by being localized, privitized, and unofficial, violate Rawls's publicity condition that is an essential part of our concept of justice. In the second part, he analyzes and criticizes the role that prospective payment mechanisms such as health maintenance organizations (HMOs), diagnosis-related groups (DRGs), and Great Britain's National Health Service play as invisible rationing mechanisms. He suggests that if HMOs could be structured so as to satisfy the publicity condition, a national system of HMOs could achieve cost containment objectives. In the third part of his paper, Fleck describes such a system of HMOs in detail, and assesses it from the perspective of justice.     

The role of human T-lymphotropic virus type 1 (HTLV-1)-infected dendritic cells in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis

The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4(+) T cells and CD8(+) T cells in a viral dose-dependent manner. However, the proliferation level of CD4(+) T cells was five- to sixfold higher than that of CD8(+) T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4(+) T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4(+) and CD8(+) T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.     

HTLV-1感染T细胞克隆扩增和转化在成人T细胞白血病表达分析

摘要 目的：探究人类T细胞白血病1型病毒（Human T-cell leukemia virus type,HTLV-1）感染的T细胞克隆扩增和转化在成人T细胞白血病（AdultT-cellleukemia,ATL）中的表达分析,探究HTLV-1在T淋巴细胞中发生克隆扩增和转化的机制,为ATL的临床治疗提供理论基础。方法：选择2015年2月至2018年2月于我院接受治疗的38例ATL患者为研究对象,按照其病程差异将其分为急性ATL组（20例）和慢性ALT组（18例）,分别采集其血样并检测两组患者血样中HTLV-1病毒载量的差异性,对比两组患者样本中Tax蛋白和HMGB1蛋白的表达情况,并就两组患者血样中肿瘤坏死因子（tumor necrosis factor,TNF-α）、癌胚抗原（carcinoembryonic antigen,CEA）的水平进行对比。结果：（1）急性ATL组患者HTLV-1病毒载量明显高于慢性ATL组患者HTLV-1病毒载量（P<0.05）;（2）对比显示,急性ATL组患者血样中Tax蛋白和HMGB1蛋白表达量明显高于慢性ATL组患者（P<0.05）;（3）急性ATL组患者中TNF-α和CEA水平均明显高于慢性ATL组患者（P<0.05）。结论：HTLV-1感染ATL患者病程的差异会影响T淋巴细胞的克隆扩增和转化进程,分析其机制可能与HTLV-1能够调控Tax蛋白和HMGB1表达有关。     

Public health and public medical care

This paper deals briefly with the historical development of the major movements and organizations dedicated to the preservation of the health and security of the American people. Statements of various national organizations on the need for integration of these various services for the protection of the indigent are presented, and the experience of one county department in San Mateo which operates a completely integrated department of public health and welfare is reviewed, giving the pros and cons of the operation of a number of disciplines through a single administration. The major advantage of an integrated department of this kind is that all the services having to do with human needs-the needs arising from emotional distress, economic reverses or illness-are combined under the direction of a physician. It is probable that failure of the health discipline to provide such services was a factor in the presentation of the Wagner Act in 1938 and the Wagner-Murray-Dingell Bill in 1943. Continued close cooperation between the various disciplines devoted to the protection of the health and welfare of American citizens can help in solving some of the current problems.