The immune response of naive CD4 T cells to influenza virus is initiated in the draining lymph nodes and spleen, and only after effectors are generated do antigen-specific cells migrate to the lung which is the site of infection. The effector cells generated in secondary organs appear as multiple subsets which are a heterogeneous continuum of cells in terms of number of cell divisions, phenotype and function. The effector cells that migrate to the lung constitute the more differentiated of the total responding population, characterized by many cell divisions, loss of CD62L, down-regulation of CCR7, stable expression of CD44 and CD49d, and transient expression of CCR5 and CD25. These cells also secrete high levels of interferon γ and reduced levels of interleukin 2 relative to those in the secondary lymphoid organs. The response declines rapidly in parallel with viral clearance, but a spectrum of resting cell subsets reflecting the pattern at the peak of response is retained, suggesting that heterogeneous effector populations may give rise to corresponding memory populations. These results reveal a complex response, not an all-or-none one, which results in multiple effector phenotypes and implies that effector cells and the memory cells derived from them can display a broad spectrum of functional potentials.
BackgroundDestruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage.Methodology/Principal FindingsMice pre-treated with PCN, independent of any specific viral antigens, were protected against both sub-lethal and lethal doses of two different influenza viruses, a mouse-adapted SARS-coronavirus, or mouse pneumovirus. Treatment with PCN significantly increased survival and was marked by enhanced viral clearance, accelerated induction of viral-specific antibody production, and significant decreases in morbidity and lung damage. The enhanced protection appears to be dependent upon the prior development of inducible bronchus-associated lymphoid tissue (iBALT) in the lung in response to the PCN treatment and to be mediated through CD4+ T cell and B cell dependent mechanisms.Conclusions/SignificanceThe immunoprophylactic strategy described utilizes an infection-independent induction of naturally occurring iBALT prior to infection by a pulmonary viral pathogen. This strategy non-specifically enhances primary immunity to respiratory viruses and is not restricted by the antigen specificities inherent in typical vaccination strategies. PCN treatment is asymptomatic in its application and importantly, ameliorates the damaging inflammation normally associated with the recruitment of immune responses into the lung.
This article describes the association between drug and alcohol use during sexual activity and high-risk sex for AIDS. Data to test this association are drawn from a prospective study of the behavioral changes made by gay men in San Francisco in response to the AIDS epidemic. Findings drawn from the May, 1984 and May 1985 waves of data collection are described. The cross-sectional analysis showed that use of particular drugs during sex, the number of drugs used during such activity, and the frequency of combining drugs and sex are all positively associated with risky sexual activity for AIDS. The retrospective data showed that men who currently abstained from combining drug use with sexual activity were likely to have been at no risk for AIDS over two measurement points during the previous year. The men who currently combined drug use with sex were most likely to have a history of high-risk sexual activity over the previous year. These findings show a strong relationship between drug and alcohol use during sex and non-compliance with safe sex techniques to prevent the spread of AIDS. Implications of this relationship for AIDS health education efforts are discussed.
A national probability survey of human immunodeficiency virus (HIV)-related risk factors among the general heterosexual population, the National AIDS (acquired immunodeficiency syndrome) Behavioral Surveys, has obtained data from 10,630 respondents. Data are presented on the prevalence of HIV-related risks in the general heterosexual population, on the distribution of the three largest risk groups across social strata, and on the prevalence and distribution of condom use among heterosexuals reporting a risk factor. Between 15 and 31 percent of heterosexuals nationally and 20 and 41 percent in cities with a high prevalence of AIDS reported an HIV risk factor. Condom use was relatively low. Only 17 percent of those with multiple sexual partners, 12.6 percent of those with risky sexual partners, and 10.8 percent of untested transfusion recipients used condoms all the time. Overall, the results suggest that current HIV prevention programs have, to a very limited extent, reached those heterosexuals with multiple sexual partners but have failed to reach many other groups of the heterosexual population at risk for HIV. New public health strategies may be needed for these specific risk groups.
This study examined the inflammation, lung function impairment, and immune protection associated with either wild-type or interferon (IFN)-gamma-deficient Tc1- or Tc2-CD8 effector cells responding to influenza pneumonia. The adoptive transfer of influenza hemagglutinin-specific Tc1 effectors afforded protection and elicited only minimal impairment of lung function. IFN-gamma-deficient Tc1 effector cells were equally protective, but were associated with an eosinophil influx and slightly more lung function impairment early in the response. Relative to Tc1, Tc2 effector cells were less protective, elicited an eosinophil influx and a greater impairment of lung functions. IFN-gamma-deficient Tc2 effector cells were not protective and were associated with the severest impairment of lung function throughout the response, an accumulation of neutrophils, and extensive pulmonary vasculitis and alveolar hemorrhaging. Deletion of IFN-gamma was associated with a delay in effector cell recruitment and the elicitation of a more intense inflammatory response that resulted in more severe lung function impairment in the recipients of either Tc1 or Tc2 IFN-gamma-deficient effector cells. Thus, during influenza infections, IFN-gamma production by the responding CD8 T cells is associated with effector cell recruitment and mitigation of the associated inflammation and of the resulting impairment in lung functions but is not necessary for optimal protection.
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