Recurrence of allergic rhinitis, previously alleviated with allergen immunotherapy, after autologous bone marrow transplant.

BACKGROUND: Several associations between immunoglobulin E and bone marrow transplantation (BMT) have been reported. OBJECTIVE: A patient whose allergic rhinitis (AR) resolved after allergen immunotherapy (AIT) but recurred after the patient received an autologous BMT is reported. METHODS: Allergy skin tests were performed before AIT began and after 4 years of therapy. Skin tests were repeated after a recurrence of symptoms 6 years later after an autologous BMT for breast cancer. RESULTS: Six years of AIT led to a near complete resolution of AR symptoms. Skin tests showed a marked reduction in reactivity to allergens in the AIT. After an additional 6-year symptom-free interval off AIT, symptoms returned after the BMT. Repeat skin tests showed a marked increase in reactivity. CONCLUSIONS: Patients reconstituting their immune systems after autologous BMT may have a recurrence of AR previously suppressed with AIT.     

The rate of systemic reactions to immunotherapy injections is the same whether or not the dose is reduced after a local reaction.

BACKGROUND: Even though no studies have shown that local reactions to immunotherapy injections predict subsequent systemic reactions, many protocols continue to call for dose adjustments after local reactions. OBJECTIVE: To determine whether the rate of systemic reactions to immunotherapy injections is affected by dose adjustment after local reactions. METHODS: In our clinic before March 1999, if a patient had a local reaction to an immunotherapy injection, an adjustment was made to repeat or reduce the next dose. From March 1999 on, no such adjustments were made. At our outlying clinics, the adjustment protocol continued. A retrospective review was conducted for shots given from March 1997 to February 2001, recording whether an immunotherapy visit resulted in a systemic reaction. RESULTS: In our clinic, there were 3,250 shot visits from March 1997 to February 1999 (adjustment protocol) and 4,692 visits from March 1999 to February 2001 (no adjustment protocol). The systemic reaction rate during the 2 periods was not different (1.11% vs 0.85%, P = .29). In the outlying clinics, there were 1,138 shot visits from March 1999 to February 2001 (adjustment protocol), and the systemic reaction rate was not different than in our clinic (no adjustment protocol) (0.88% vs 0.85%, P = .86). CONCLUSIONS: The rate of systemic reactions to immunotherapy injections is the same whether or not the dose is adjusted after a local reaction. These dose adjustments are thus unnecessary, and eliminating them lessens chances for errors and decreases the number of shots required to reach a therapeutic dose.     

Limiting dilution analysis reveals the precursors of interleukin-4-producing CD4+ cells induced by protein immunization.

Although cytokine-producing T cells play a key role in the response to vaccination, they are not always revealed by antigen stimulation of primed lymphoid cells in vitro. In this study, mice were immunized subcutaneously with alum-precipitated keyhole limpet haemocyanin (KLH) in adjuvant to activate interleukin-4 (IL-4)-producing CD4+ T cells. IL-4 mRNA was the dominant cytokine mRNA species found in draining lymph nodes (LN) 7 days after immunization and its levels were increased after in vitro stimulation with KLH for 24 hr. IL-4 protein, on the other hand, was not detected in the supernatants of such antigen-stimulated cultures. The presence of T cells primed for IL-4 production was nevertheless suggested by the findings that primed LN cells produced low IL-4 titres in response to anti-CD3 antibody, whereas normal LN cells did not, and primed CD4+ LN cells produced readily detectable IL-4 levels in response to antigen after one or more cycles of in vitro restimulation. Culture at limiting dilution showed that 1-2% of 7 day KLH-primed CD4+ LN cells were clonogenic and specific for KLH without prior expansion in vitro, and that this frequency was markedly increased by repeated stimulation in bulk culture. Most clonogenic cells in primed LN gave rise to IL-4-secreting clones and a smaller number gave rise to interferon-gamma (IFN-gamma)-producing clones. The precursor frequency of IL-4-producing CD4+ cells in primed LN and the average IL-4 titre per cloned cell support the conclusion that these two parameters account for the low levels of IL-4 produced in bulk culture by LN cells from immunized mice.     

Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granulocyte-macrophage-, and multi-CSFs.

After infection of mice with Listeria monocytogenes, elevated levels of colony-stimulating factors (CSFs) in the serum were quantitated by six different assays: ability to stimulate colony formation, the proliferation of 2 suspension of bone marrow cells (both measuring total colony-stimulating activity), a radioimmunoassay for macrophage-CSF (CSF-1), the WEHI-3B differentiation assay for granulocyte-CSF, and proliferation of 32D-c1-3 and FDC-P1 cell lines (specific for multi-CSF and either multi- or granulocyte-macrophage-CSFs, respectively). The great bulk of serum colony-stimulating activity represented macrophage- and granulocyte-CSFs, with small but measurable amounts of granulocyte-macrophage-CSF. The degree of elevation of serum CSF depended on the infecting dose used and the numbers of bacteria growing in the spleens and livers of the two mouse strains compared, i.e., L. monocytogenes-resistant C57BL/10 and susceptible BALB/cJ. The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.     

Trans-ACPD reduces multiple components of synaptic transmission in the rat hippocampus.

Activation of metabotropic quisqualate receptors by trans-ACPD (trans-1-aminocyclopentane-1,3-dicarboxylic acid) caused a reduction in the amplitude of the synaptic response elicited by stimulation of the Schaffer collateral projection and recorded intracellularly from area CA1 in slices of rat hippocampus. Pharmacological agents were used to isolate components of the response mediated by N-methyl-D-aspartate (NMDA) receptors, non-NMDA receptors, and gamma-aminobutyric acid (GABA) receptors. Each of these components was reduced during the trans-ACPD application. These results indicate that one subtype of glutamate receptor may be able to decrease the synaptic efficacy of other subtypes and may provide an important means for balancing the synaptic enhancement processes often studied in the hippocampus.     

Practice-dependent modulation of neural activity during human sensorimotor coordination: a functional Magnetic Resonance Imaging study

We investigated the degree to which differences in the pattern of blood oxygen level dependent activity (BOLD) between syncopated and synchronized coordination patterns are altered by practice. Baseline levels of BOLD activity were obtained from eight subjects while they syncopated or synchronized with an auditory metronome at 1.25 Hz. Subjects then practiced syncopation at the same rate for four consecutive sessions. Post practice scans of the two coordination patterns were then performed. Before practice, baseline syncopation activated a much broader network of both cortical and subcortical regions than synchronization that included Supplementary Motor Area (SMA), bilateral putamen, left thalamus, bilateral superior temporal gyrus as well as the vermis. This pattern of activity is hypothesized to reflect the extra timing and attention requirements of syncopation. After practice, activity in superior temporal gyrus and vermis were no longer observed during syncopation reflecting a reduction in the need for attention and the use of sensory feedback for guiding behavior. Surprisingly, post practice synchronization resulted in additional significant activations in SMA, inferior frontal gyrus and superior temporal gyrus as well as small activations in bilateral putamen. Practice with the more difficult syncopation task thus had a dual effect of decreasing the number of active regions during syncopation and increasing the number of active regions during synchronization. Since overt syncopation performance did not change significantly as a result of practice, these observed neural changes appear to be due to context- and history-dependent factors, rather than behavioral learning per se.     

The fluorolysis assay,a highly sensitive method for measuring the cytolytic activity of T cells at very low numbers

We have developed a highly sensitive cytolysis test, the fluorolysis assay, as a simple nonradioactive and inexpensive alternative to the standard 51Cr-release assay. P815 cells were stably transfected with a plasmid expressing the enhanced green fluorescent protein (EGFP) gene. These target cells were coated with or without cognate peptide or anti-CD3 Ab and then incubated with CD8(+) T cells to allow antigen-specific or nonspecific lysis. The degree of target cell lysis was measured using flow cytometry to count the percentage of viable propidium iodide(-) EGFP(+) cells, whose numbers were standardized to a reference number of fluorochrome-linked beads. By using small numbers of target cells (200-800 per reaction) and extended incubation times (up to 2 days), the antigen-specific cytolytic activity of one to two activated CD8(+) T cells of a CTL line could be detected. The redirected fluorolysis assay also measured the activity of very few (> or =6) primary CD8(+) T cells following polyclonal activation. Importantly, antigen-specific lysis by small numbers (> or =25) of primary CD8(+) T cells could be directly measured ex vivo. This exquisite sensitivity of the fluorolysis assay, which was at least 8-33-folds higher than an optimized 51Cr-release assay, allows in vitro and ex vivo studies of immune responses that would otherwise not be possible due to low CTL numbers or frequencies.     

Monoclonal antibodies with neutralizing activity segregate isolates of bovine viral diarrhea virus into groups

Summary Isolates of bovine viral diarrhea (BVD) virus were differentiated by monoclonal antibodies (MoAbs) reactive with the 56kD viral polypeptide. Patterns of neutralizing activity of the MoAbs indicate that multiple epitopes are involved in virus neutralization.