The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions.

T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56lck. Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca2+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

The effect of exogenous interleukin 2 (IL 2) on lymphokine production by T lymphocytes was examined in two systems: the secretion of macrophage-activating factor (MAF) and interferon (IFN) by cloned long-term T cell lines, and a limiting dilution system for estimating the frequency of precursors of MAF-secreting cells in normal spleen. An IL 2-containing, MAF- and IFN-free supernatant from the EL-4 thymoma (EL-4 SN) significantly enhanced release of MAF and IFN by mitogen- or antigen-stimulated, cytolytic or noncytolytic T lymphocyte clones directed against alloantigens or Moloney leukemia virus-associated antigens. Highly purified IL 2 produced equivalent enhancement as EL-4 SN in cultures of alloreactive clones stimulated with concanavalin A. Kinetics experiments showed that EL-4 SN increased both the rate and duration of MAF release by T cell clones. EL-4 SN also increased MAF production when added during restimulation of limiting dilution cultures of positively selected Lyt-2+ and Lyt-2- C57BL/6 splenic T lymphocytes activated against DBA/2 alloantigens. This enhancement resulted in a threefold increase in the apparent precursor frequency of MAF-secreting cells among Lyt-2+ lymphocytes, but did not affect the frequency among Lyt-2- cells. Additional analysis indicated that average MAF production in cultures of Lyt-2-+ cells was sixfold lower than in cultures of Lyt-2- cells, and hence that EL-4 SN allowed detection of a significant proportion of Lyt-2+ cell cultures secreting low levels of MAF. Under these improved conditions, the MAF assay detected the majority of responding Lyt-2+ and Lyt-2- lymphocytes.

Transformation of baby mouse kidney epithelial cells by human papillomavirus (HPV) type 16 is dependent both upon the cooperating oncogene and on the hormonal conditions after transfection. With v-fos as the oncogene, the transformed cells require glucocorticoid hormone, such as dexamethasone, for proliferation. This requirement is lost on continued passage of cell lines, and the cells become dexamethasone independent. Steroid-independent cell lines are also produced by growth of the HPV16/v-fos cells in 17 beta-estradiol following transfection, but cell lines produced in this manner showed no subsequent requirement for estradiol or dexamethasone. Expression of the c-myc proto-oncogene was measured in dexamethasone-dependent and independent cell lines. Dexamethasone-dependent cell lines all exhibited low level c-myc expression, but this markedly increased in the cell lines that had become dexamethasone independent as a result of continued in vitro growth. The low level of c-myc expression in some early passage dexamethasone-dependent cell lines appears to be associated with rearrangement of the c-myc locus, whereas late passage dexamethasone-independent cell lines contain amplified c-myc sequences. Dexamethasone-independent cell lines derived by growth in 17 beta-estradiol showed higher levels of c-myc expression, together with higher c-myc copy number, than dexamethasone-dependent lines. Taken together, these studies indicate that the steady-state level of c-myc expression affects the continued requirement of HPV16-transformed cells for dexamethasone.

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