W W Cruikshank

Chemoattractant lymphokines specific for the helper/inducer T-lymphocyte subset☆☆☆

The cellular content of T-lymphocyte-rich inflammatory sites is dependent in part on the in situ elaboration of chemoattractant factors. We have previously described three T-lymphocyte-specific chemoattractant lymphokines; a chemokinetic factor, lymphocyte chemoattractant factor (LCF, MW 56,000), and two distinct lymphocyte migration inhibitory factors (LyMIF75K, MW 75,000; and LyMIF35K, MW 35,000). These factors are produced by human T cells in response to antigen, concanavalin A, or histamine stimulation. In this communication, we report that LCF and LyMIF35K are produced by OKT8+ (suppressor/cytotoxic) and OKT4+ (helper/inducer) lymphocytes, respectively, and are selectively chemoattractant for the OKT4+ lymphocyte subset. LyMIF75K is produced by OKT4+ cells and inhibits both OKT4+ and OKT8+ lymphocyte migration. Production of LCF and LyMIF35K by infiltrating lymphocyte subsets may be one mechanism whereby unactivated helper/inducer T lymphocytes are selectively recruited to sites of inflammation.

Characterization of regulatory T cells in urban newborns

BackgroundIn the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers.MethodsTreg numbers, expression, and suppressive function were quantified in subjects recruited prenatally from neighborhoods where ≥ 20% of families have incomes below the poverty line. Proportion of Treg cells and expression of naïve (CD45RA) or activated (CD45RO, CD69, and HLA-DR) markers in CD4+T cells was measured by flow cytometry. Treg suppressive capacity was determined by quantifying PHA-stimulated lymphocyte proliferation in mononuclear cell samples with and without CD25 depletion.ResultsIn an urban cohort of 119 newborns and 82 mothers, we found that newborns had similar number of cells expressing FOXP3 as compared to the mothers but had reduced numbers of CD4+CD25+bright cells that predominantly expressed the naïve (CD45RA) rather than the activated/memory (CD45RO) phenotype found in the mothers. Additionally, the newborns had reduced mononuclear cell TGF-β production, and reduced Treg suppression of PHA-stimulated lymphocyte proliferation compared to the mothers.ConclusionU.S. urban newborns have Treg cells that express FOXP3, albeit with an immature phenotype and function as compared to the mothers. Longitudinal follow-up is needed to delineate Treg cell maturation and subsequent risk for atopic diseases in this urban birth cohort.

Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City and Suburban Infants

Abstract Background.u2003The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct. Methods.u2003We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction. Results.u2003Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%–21%), compared with Madison (6%). Conclusions.u2003These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.

Relation between stress and cytokine responses in inner-city mothers.

BACKGROUNDnWomen in poor urban neighborhoods have high rates of stress and allergic diseases, but whether stress or stress correlates such as depression promote inflammatory and type 2 cytokine responses is unknown.nnnOBJECTIVEnTo examine associations among external stressors, perceived stress, depression, and peripheral blood mononuclear cell cytokine responses of mothers enrolled in the Urban Environment and Childhood Asthma Study and test the hypothesis that stress would be positively associated with type 2 and selected proinflammatory (tumor necrosis factor-α and interleukin-8) responses.nnnMETHODSnQuestionnaire data from mothers living in 4 inner cities included information about external stress, stress perception, and depression. The external stress domains (interpersonal problems, housing, and neighborhood stress) were combined into a Composite Stressor score. Peripheral blood mononuclear cells were stimulated exxa0vivo and cytokine responses to innate, adaptive, and polyclonal immune stimuli were compared with stress and depression scores for 469 of the 606 study participants.nnnRESULTSnThere were no significant positive associations between Composite Stressor scores, perceived stress, or depression scores and proinflammatory or type 2 cytokine responses, and these findings were not modified by allergy or asthma status. There were some modest associations with individual stressors and cytokine responses, but no consistent relations were noted. Depression was associated with decreased responses to some stimuli, particularly dust mite.nnnCONCLUSIONnComposite measurements of stressors, perceived stress, or depression were not positively related to proinflammatory or type 2 cytokine responses in these young urban women. These data do not support the hypothesis that these factors promote cytokine responses associated with allergy.nnnTRIAL REGISTRATIONnClinicalTrials.gov, identifier NCT00114881.

Measurement of Interleukin 16

Interleukin 16 (IL‐16) is a chemoattractant immunomodulatory cytokine that initiates its cellular responses through interaction with membrane‐expressed CD4. The protein may be detected by a number of methods; the choice of protocol will depend on the ultimate object of a particular experiment. The first method presented is the use of ELISA to measure IL‐16 in cell culture supernatants or biological fluids. For some applications, such as identification of IL‐16 in an unknown fluid or medium or direct assessment of its bioactivity, functional assays of IL‐16‐induced responses may be more appropriate. The chemotactic effects of IL‐16 on CD4+ T cells and its specific inhibition may be measured using anti‐IL‐16 antibodies; the same approach may also be applied to monocytes or eosinophils. Another effect of IL‐16 is the induction of CD25, which can be assayed using immunological staining. Finally, cell cycle progression in target cells can be measured by the incorporation of radiolabeled thymidine and confirmed by inhibition with neutralizing antibody.