Substance Abuse and Rural Appalachian Pediatric Trauma in West Virginia.

Introduction: Rural Appalachia is endemic to issues such as substance abuse, poverty, and lack of community support, all of which negatively influence health outcomes. The incidence of pediatric trauma as it relates to substance abuse is of concern in the region, where the rate of positive drug screens in pediatric trauma cases is higher than national average.

Methods: The West Virginia statewide pediatric trauma database was analyzed in a retrospective cohort study for the years 2009-2019.

Involvement of "accessory" and antigen receptor molecules in human helper T cell clone activation studied by monoclonal antibody inhibition.

The requirements for activation of autocrine proliferation in human helper T cell clones (Th-TCC) by allogeneic cells were examined in monoclonal antibody (MoAb) blocking studies. Stimulation was not blocked by CD4, CD5, CD6, CD7, or CD45 MoAbs, despite high levels of expression of these antigens on the TCC. Only CD2 and CD11a (LFA-1) MoAbs blocked activation, the latter only when peripheral blood mononuclear cells (PBMCs) and not B-lymphoblastoid cell line (B-LCL) cells were used at stimulators.

Prevention of human helper T-cell clone activation by cyclosporin A also blocks secretion of granulocyte/macrophage colony stimulating activity.

Cyclosporin A (CsA) blocks stimulation and growth of alloreactive T helper cell clones (Th-TCC), even in the presence of exogenous Interleukin-2 (IL-2). To examine whether this might reflect a generalised inhibition of cytokine production by these cells, their production of granulocyte/macrophage colony-stimulating factors (GM-CSF), thought not to be involved in the autocrine proliferation of the clones themselves, was investigated. Contrary to the prediction that only pathways relevant to T cell clonal expansion would be blocked by CsA, it was found that this immunosuppressive substance exerted a profound inhibitory activity on GM-CSF secretion, even in the presence of exogenous IL-2.

Regulation of allospecific suppressive cell generation in vitro.

Control of the generation of suppressive cells (SC) in allogeneic mixed lymphocyte cultures (MLC) has been re-investigated. Cells taken from 3-6 days old ("early", e-MLC) suppressed lymphocyte proliferative responses when transferred to a second MLC. Suppression was not allospecific, nor restricted to the autologous responder.

Cyclosporin A blocks the generation of alloindifferent but not of allospecific suppressive cells.

The induction of alloantigen-indifferent, MHC unrestricted suppressive cells (SC) early on in human mixed lymphocyte culture (MLC) or after stimulation with suppressive T cell clones was blocked in a dose-dependent fashion by cyclosporin A (CsA). This was not prevented by the addition of the following defined lymphokines: interleukin (IL) -1, -2, -4, -5, interferon-tau or GM-CSF. The addition of MLC-conditioned medium as a source of multiple lymphokines including IL-3 also failed to reconstitute suppressive activity in the presence of CsA.