Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway.

Human T-cell clones and anti-T-cell-receptor antibodies (clonotypic) directed at surface receptors for antigen (T3-Ti molecular complex) as well as anti-interleukin 2 (IL-2) and anti-IL-2-receptor antibodies were utilized to investigate the mechanism by which alloantigens or antigen plus self-major histocompatibility complex (MHC) (i.e., physiologic ligand) trigger specific clonal proliferation. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand, enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor cross-linking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors.     

Major depression and drug disorders in adolescence: general and specific impairments in early adulthood.

OBJECTIVE: To identify adulthood impairments associated with major depression and drug disorders in adolescence, distinguishing between general impairments for both disorders and specific impairments for each disorder. METHOD: Within a longitudinal community study (N= 365), the Diagnostic Interview Schedule provided 1-year diagnoses of major depression and drug abuse/dependence at age 18. At age 21, current functioning was assessed. RESULTS: Adolescents with either depression or drug disorders had substantial deficits in later functioning, with few impairments shared in common. General areas of impairment included lower global functioning, externalizing behavior problems, and suicidal behaviors. Difficulties specific to depression encompassed multiple internalizing problems: interpersonal difficulties, decreased psychological well-being, career dissatisfaction, and active major depression at age 21. For males only, overall poor health was also a specific depression outcome. Age 21 problems unique to drug disorders included lower likelihood of post-high school education, being fired, and active drug disorders. Males, but not females, were also more likely to report antisocial behaviors in adulthood. CONCLUSIONS: Despite several significant commonalities, including suicide attempts, deficits associated with depression and drug disorders were primarily specific, suggesting distinct trajectories. Results highlight the need for specific follow-up services to alleviate continuing problems associated with these disorders.     

CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment,but elicit divergent functional activities

Interaction trap cloning was used to identify a CD2 cytoplasmic tail-binding protein termed CD2BP3. CD2BP3 is the major RNA splice variant of the CIN85 locus in human T lymphocytes, lacking SH3A, the first of three SH3 domains found in CIN85, but retaining SH3B, SH3C, a proline-rich domain and C-terminal coiled coil. CD2BP3 has 35% amino acid identity to CMS, a structurally related protein binding to the same highly conserved segment of the CD2 tail and known to be involved in T cell polarization/cytoskeletal interactions. Unlike CMS, however, CD2BP3 does not co-localize with F-actin and binds p130(Cas) weakly, if at all. Moreover, CIN85/CD2BP3 proteins are readily degraded by TCR cross-linking, consistent with the presence of a PEST sequence C-terminal to SH3C. CIN85 SH3A and CIN85/CD2BP3 SH3B bind to proline-rich segments within CIN85/CD2BP3 themselves as evidenced by mAb accessibility analysis and protein interaction studies including c-Cbl binding. This form of intramolecular regulation is not manifest by CMS. CMS and CIN85 activities are antagonistic, while the functions of CIN85 and CD2BP3 are also distinct. Thus, CD2-mediated adhesion, signaling and cell motility are regulated in a highly complex manner.     

Tenography around the ankle and introduction of a new technique

Tenography; the injection of radiopaque contrast medium into a tendon sheath, is being done with increasing frequency for diagnosis of painful conditions surrounding the ankle because it provides a permanent radiographic record of the extent of soft tissue pathology. The authors discuss the indication for tenography, the precautions that are necessary, and the techniques used to introduce the contrast material. They advocate a technique that greatly improves the accuracy of sheath penetration.     

Functional and phenotypic studies of Japanese adult T cell leukemia cells.

The cell surface marker profile and functional analysis of peripheral blood lymphocytes from 11 Japanese adult T cell leukemia patients were studied. The phenotypic analysis of Japanese adult T cell leukemia (ATL) cells by a series of 13 monoclonal antibodies showed that all ATL cells are anti-T4 reactive but some differ in their expression of T3, T11, and T12 antigens. Thus, considerable phenotypic heterogeneity exists in these populations of leukemia cells. When analyzed in functional assays, ATL cells were suppressive when added to a pokeweed mitogen- (PWM) driven Ig synthesis system. However, the suppression mechanism seemed to be more complex than originally conceived. ATL cells examined in this study seem to function mainly as an inducer of suppressor cells, and as such, activate normal T8 precursors of suppressor cells rather than function as suppressor effector cells. In addition, no evidence was obtained to suggest that suppression of PWM-stimulated IgG synthesis was mediated by natural killer (NK) activity of ATL cells. Rather, ATL cells seem to be markedly deficient in NK activity. These studies suggest that the majority of ATL cells tested are representative of and seem to be the leukemic counterparts of the T4+ suppressor inducer subset.