T cell redistribution kinetics after secondary infection of BALB/c mice with respiratory syncytial virus.

BALB/c mice were infected intranasally with live respiratory syncytial virus (RSV) and reinfected 4 weeks later. At regular intervals thereafter groups of animals were killed and T cell subsets were determined in blood, spleen and bronchoalveolar lavage (BAL) with flow cytometry employing T cell subset-specific MoAbs. Total lymphocyte counts in the peripheral blood decreased 1-3 days after infection, returning to preinfection levels on day 8 (P = 0.0111). Simultaneously, a marked increase of lymphocytes was noted in the BAL, reaching a maximum at day 8 (P < 0.0001). Both CD4+ and CD8+ T cells decreased in the blood on day 1-3 (P < 0.0097 and P = 0.003 respectively), and increased in the BAL progressively towards a maximum at day 8 (P < 0.0001). In BAL, CD4+ cells increased 35-fold and CD8+ cells 27-fold during the first week after reinfection. On the other hand, in the spleen a significant decline of CD4+ and CD8+ cells was noted 1 day post-infection (P = 0.0002). It is concluded that a strong T cell redistribution response among systemic and mucosal tissues occurs after reinfection with RSV. The kinetics of this response differ both quantitatively and qualitatively from the T cell response after primary infection. The magnitude of cell traffic is more pronounced in blood, spleen and BAL than after primary infection. CD4+ T cells are more intensively distributed to the lungs than after primary infection.     

Involvement of type I immune responses in swine-origin H1N1 influenza virus infection

Swine-origin H1N1 influenza virus (S-OIV) appeared in 2009 with a higher incidence rate among children. Although fever was the most common symptom, some complicated cases occurred. We evaluated the percentages of effector T cells, B cells, and regulatory T cells in peripheral blood from 5 children infected by S-OIV (1 with acute necrotizing encephalitis, 2 with pneumonia, and 2 without complications), 5 children with seasonal influenza, and 5 healthy children. We found higher percentages of T-bet(+) CD4(+)CD8(+) T cells, monocytes, and B cells, granzyme B(+) and perforin(+) CD4(+), and CD8(+) T cells in affected children with both seasonal and H1N1 influenza than in controls, whereas both groups demonstrated similar percentages of CD4(+)CD25(+)Foxp3(+) regulatory T cells. In infected children with complications we observed high percentages of perforin(+) and interferon-γ(+) CD4(+) and CD8(+) T cells associated with low percentages of T regulatory cells. Our data suggest a dysregulation of antipathogen type I immune responses in complicated S-OIV infections.     

呼吸道合胞病毒下呼吸道感染对机体细胞免疫的影响

为研究呼吸道合胞病毒（ＲＳＶ）急性下呼吸道感染（ＡＬＲＩ）的细胞免疫变化，对２５例病儿外周血白细胞介素２（ＩＬ－２）和可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平、Ｔ细胞白细胞介素２受体（ＩＬ－２Ｒ）表达率和Ｔ细胞亚群百分率进行检测。结果显示，急性期病儿外周血ＩＬ－２水平明显低于恢复期和正常对照组，Ｔ细胞ＩＬ－２Ｒ表达率亦明显降低，而ｓＩＬ－２Ｒ水平却显著增高。急性期病儿ＩＬ－２水平与Ｔ细胞ＩＬ－２Ｒ表达率和ＣＤ＋４细胞百分率呈正相关，与ｓＩＬ－２Ｒ水平和ＣＤ＋８细胞百分率呈负相关；ｓＩＬ－２Ｒ水平与Ｔ细胞ＩＬ－２Ｒ表达率呈负相关，与临床严重程度呈正相关。上述各项免疫指标异常均提示ＲＳＶ感染时机体存在细胞免疫功能紊乱。     

Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry

Acute RSV infection in infancy may produce some asthma-like symptoms and may be followed by a recurrent wheeze later in childhood. It has been proposed that RSV infection stimulates type-2 cytokine responses, resembling those found in atopy and asthma. Peripheral blood cells were obtained from RSV-infected infants (n = 30) and healthy controls (n = 10). After in vitro restimulation of the cells, intracellular IL-4 and interferon-gamma (IFN-gamma) were measured by flow cytometry. The cells from RSV-infected infants produced more IL-4 and less IFN-gamma than those from healthy controls. IL-4 production was more frequent in CD8 than in CD4 cells, and the bias toward IL-4 production was greatest in infants with mild infections, whereas IFN-gamma production increased with disease severity. Our conclusions are that RSV infection is associated with IL-4 production in peripheral T cells, and that peripheral blood in infants with severe disease may be depleted of cytokine-producing cells.     

Enhanced expression of CTLA-4 (CD152) on CD4+ T cells in HIV infection

CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Down-regulation of CD28 predominantly on CD8+ T cells has been described in HIV infection, but analysis of CTLA-4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA-4 on peripheral blood mononuclear cells (PBMC) during HIV infection. CTLA-4 was expressed only on T cells. Expression levels were significantly increased selectively on CD4+ T cells during all stages of HIV infection, while CTLA-4 expression on CD8+ T cells was always low. In contrast, after stimulation with the mitogen phytohaemagglutinin (PHA), CTLA-4 levels were strongly increased on T cells from controls but in T cells from HIV patients this response was severely impaired. Our data suggest that in HIV infection CD4+ and CD8+ T cells may be less responsive to B7 costimuli due to two different mechanisms: increase in CTLA-4 expression by CD4+ cells and down-regulation of CD28 by CD8+ cells.     

IL-2调节人外周血T淋巴细胞CTLA-4表达

目的 探讨人外周血T淋巴细胞CTLA-4的表达情况及IL-2对其表达的调节作用。方法 采用流式细胞仪定量测定人外周血T淋巴细胞内及细胞膜上CTLA-4的水平，半定量RT-PCR检测T淋巴细胞内CTLA-4mRNA的水平，并在体外用IL-2刺激T淋巴细胞后观察CTLA-4及CTLA-4mRNA水平的变化。结果 人外周血T淋巴细胞膜表面几乎不表达CTLA-4，7．6％-18．0％的T淋巴细胞有胞内表达，CD4^ T淋巴细胞表达CTLA-4的阳性比例略高于CD8^ T淋巴细胞；人T淋巴细胞可溶性形式的CTLA-4mRNA半衰期短于全长CTLA-4mRNA；IL-2可以通过诱导人T淋巴细胞CTLA-4mRNA的转录上调CTLA-4的表达，IL-2诱导的细胞多为CD25^ T淋巴细胞。结论 CTLA4多存在于人外周血T淋巴细胞内，参与T淋巴细胞活化过程的调节。IL-2的免疫抑制作用可能与其诱导T淋巴细胞内CTLA-4mRNA转录，从而上调CTLA-4的表达有关。     

Reduced activation and proliferation of human lymphocytes exposed to respiratory syncytial virus compared to cells exposed to influenza virus

Both respiratory syncytial virus (RSV) and influenza A virus (IAV) may infect human peripheral blood mononuclear leukocytes (PBMC) during the immune response to viral challenge as the cells are recruited to the respiratory tract. The current studies demonstrated differences in PBMC responses to the two viruses very early after exposure, including reduced fos protein and CD69 expression and IL‐2 production by RSV‐exposed T lymphocytes. Exposure to RSV resulted in reduced lymphocyte proliferation despite evidence of a virus‐specific T lymphocyte frequency equivalent to that for influenza virus. Reduced RSV‐induced proliferation was not due to apoptosis, which was itself reduced relative to that of influenza virus‐exposed T lymphocytes. The data indicate that differential immune responses to RSV and influenza virus are determined early after exposure of human PBMC and support the concept that the anamnestic immune response that might prevent clinically evident reinfection is attenuated very soon after exposure to RSV. Thus, candidate RSV vaccines should be expected to reduce but not prevent clinical illness upon subsequent infection by RSV. Furthermore, effective therapeutic agents for RSV are likely to be needed, especially for high‐risk populations, even after vaccine development.     

The association of CTLA-4 and HLA class II autoimmune risk genotype with regulatory T cell marker expression in 5-year-old children

Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance by suppression of autoreactive lymphocytes that have avoided thymic depletion. The defective function of Treg cells has recently attracted attention in autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and multiple sclerosis. Susceptibility to these diseases is associated with specific human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms. This study aimed to investigate the relationship between HLA class II and CTLA +49 A/G polymorphisms associated with susceptibility to T1D and the number and characteristics of Treg cells in children. Samples from 47 5-year-old children who participated in the All Babies in South-east Sweden (ABIS) follow-up study were grouped according to the presence of the T1D risk-associated HLA genotype (DQA1*0501-DQB1*0201, DQA1*0301-DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (P = 0.03) and CD4+ CD25high cells (P = 0.06) expressing intracellular CTLA-4 were detected in samples from children with CTLA-4 +49GG compared to children with the +49AA genotype. Similarly, lower percentages of CD4+ (P = 0.002) and CD4+ CD25high (P = 0.002) cells expressing CTLA-4 were observed in children positive for HLA DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 (P = 0.04 for CD4+ and P = 0.02 for CD4+ CD25high) risk haplotypes when compared to children without these alleles. The percentage of CD25high cells among CD4+ cells was correlated inversely with CTLA-4 mRNA expression in PBMC (r = -0.56, P = 0.03). Decreased levels of CTLA-4 in CD4+ and CD4+ CD25high cells in individuals with CTLA-4 and HLA class II alleles associated with T1D may contribute to the initiation and/or progression of autoimmune response.     

苦参碱对慢性乙型肝炎患者T细胞亚群的影响

目的探讨苦参碱治射液对慢性乙型肝炎患者外周血T细胞免疫的影响。方法采用SAP法检测30例慢性乙型肝炎患者外周血T细胞亚群。结果有2例感染者达到完全应答,12例部分应答,16例无应答;苦参碱治疗后外周血CD3 T细胞较治疗前明显增高,应答组CD4 T细胞显著高于无应答组。结论用苦参碱治疗慢性乙型肝炎患者可以影响患者T细胞免疫,使患者CD4 T细胞水平明显增高。     

CD8 T cell responses to influenza virus infection in aged mice

Influenza is one of the most common infectious diseases afflicting humans, particularly the elderly. The murine model has been widely employed for investigation of immunity to influenza virus infection. In this paper, we review the recent advances in understanding the diminished CD8 T cell immune response to influenza virus infection in aged mice. Possible mechanisms of impaired CD8 T cell responses with aging are addressed, including: (1) the role of dendritic cells (DCs); (2) the effect of age-associated changes in the T cell repertoire; and (3) the interactions with CD4 T cells, including T regulatory (Treg) cells and CD4 T helper cells. The aged murine model of the CD8 T cell response to influenza virus is helping to elucidate the mechanisms of immunosenescence which can lead to therapeutic improvements in the primary CD8 T cell response to new infections, as well as the development of new strategies for immunization to prevent influenza in the elderly.     

Induction of CD4 T cell proliferation and in vitro Th1-like cytokine responses to measles virus

Mechanisms that lead to induction of life-long immunity to measles virus (MV) are poorly understood. In the present study, we have assessed the activation, proliferation and cytokine secreting function of peripheral blood T cells from MV immune individuals. Expression of cell blastogenesis markers, such as increased forward light scatter and CD38 expression, peaked 5-7 days after infection of peripheral blood mononuclear cells (PBMC) with the live attenuated Edmonston strain of MV. Subset analysis revealed that both CD3- and CD3+ cells expressed activation markers but that the CD3+ T cells predominated late in the culture period corresponding to maximal proliferation and cell recovery. The majority of CD3+ T cells consisted of CD4+CD8- cells. IFN-gamma and IL-4 production similarly showed optimal production late in culture. Depletion of CD4 cells prior to culture and MV stimulation completely abrogated both IFN-gamma and IL-4 production, whereas depletion of CD8 cells did not diminish production, suggesting that CD4+CD8- T cells were principally involved in production of these cytokines. Finally, optimal IFN-gamma production was elicited at high MV doses and IL-4 at much lower doses. These results suggest that among MV immune individuals, in vitro responses to measles are dominated by CD4+ T cells that, depending on antigen dose, primarily produce a Th1-like and, to a lesser extent, a Th1/Th2-mixed pattern of cytokine release.     

Immune responses during acute and chronic infection with hepatitis C virus

Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.     

Respiratory syncytial virus infection suppresses IFN-gamma production of gammadelta T cells

The immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. gammadelta T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-gamma and interleukin (IL)-4 by mitogen-stimulated gammadelta T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. gammadelta T cells from RSV-infected infants had a lower proportion of IFN-gamma-producing cells (median, 4.00%; range, 0.58-6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13-2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43-61.21%; P < 0.01, median, 0.00%; range, 0.00-0.00%; P < 0.05) in the acute phase. By contrast, differences in cytokine production by total CD3+ T cells did not differ significantly between patient groups. Thus, reduced IFN-gamma-production by gammadelta T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-gamma-producing gammadelta T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02-1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25-10.98%; P < 0.005). Cytokine production by gammadelta T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.     

禽流感H5N1亚型病毒感染BALB/c小鼠的免疫应答

目的 研究禽流感H5N1病毒感染BALB/c小鼠后对宿主细胞免疫功能和细胞因子水平变化的影响,探讨禽流感H5N1病毒感染哺乳动物的免疫发病机制.方法 选用鹅源禽流感H5N1病毒感染BALB/c小鼠,采用流式细胞仪检测血液和脾脏T淋巴细胞及其亚群的变化,采用ELISA检测血液中细胞岗子(IFN-γ、TNF-α、IL-4、IL-18、IL-10、IL-2)及禽流感H5N1病毒特异性抗体的变化.结果 禽流感H5N1病毒感染可引起对宿主短暂的、可恢复的细胞免疫功能损伤:血液CD3+、CD4+、CD8+ T淋巴细胞数量于染毒后第2～4天下降(第4天为最低值),脾脏T淋巴细胞数最于染毒后第5～8天下降(第6天为最低值),然后均逐渐恢复到正常水平.染毒后血液细胞因子变化表现为:血清IFN-γ、TNF-α水平下降,IL-4、IL-18、IL-10水平上升,IL-2水平无明显变化.从感染第7天开始检测H5N1禽流感特异性抗体为阳性,抗体水平逐渐升高至实验结束的感染第14天.结论 H5N1禽流感病毒感染可引起宿主T细胞免疫功能低下是其主要的免疫病理改变之一,细胞因子表达失平衡或过多的表达都可能对宿主产生免疫病理损伤.

Abstract：

Objective To study the cell immunity and eytokines responses to avian influenza A H5N1 virus infections in a BALB/c model to better understand the pathogenesis of H5N1 avian influenza disease. Methods Two hundred and twenty BALB/c mice of the infected group were inoculated with 0.1 ml (10-4.875 TCID50) of A/Goose/Guangdong/NH/2003 ( H5N1 ) virus intra-nasally. Fifty control mice received noninfectious allantoic fluid and another fifty control mice received normal sodium. Blood and spleen samples were collected from the live mice every 24 h during the 14 d post-infection. The changes of CD3 + T cells , CD4 + T cells, CD8 + T cells for cell immunity in blood circulation and spleen were detected by flow cytometry. And the cytokines and antibody responses in blood circulation were detected by ELISA. Necropsy was performed on mice that died during the experiment and those euthanized at end of study. Results Avian influenza A( H5N1) virus infections can make damages to the cell immune system transiently. The CD3 + T cells, CD4 + T cells, CDS + T cells declined at 24 days post infection in blood circulation and declined at 5-8 days in spleen, then recovered to the normal level gradually. The eytokines responses to the infections can be detected: the level of IFN-γ,TNF-α declined, IL-4, IL-18, IL-10 increased, and IL-2 changed little. The antibody increased rapidly from day 7 post infection until the end of the study (day 14 post infection). Conclusion Collectively, avian influenza A(H5N1) virus can cause cell immunity deficiency and an imbalance in the level of eytokines, which may contribute to the unusual severity of disease caused by the H5N1 avian influenza virus.     

Preferential loss of Th17 cells is associated with CD4 T cell activation in patients with 2009 pandemic H1N1 swine-origin influenza A infection

Very limited evidence has been reported on host T cell responses to the pandemic H1N1 swine-origin influenza A virus (S-OIV) infection in humans. Therefore, we investigated the proportions of peripheral T cell subsets and analyzed the relationship of T helper subset changes with T cell activation during this infection. We found that these S-OIV-infected patients exhibited rapid lymphopenia, T cell activation and preferential loss of Th17 subset at the early stage of acute infection. Statistical analysis indicated that CD4 depletion and loss of Th17 cells, rather than Th1 or Treg cells, were correlated with CD4 T cell activation. More importantly, up-regulated IFN-α likely contributed to the functional loss of Th17 cells. Thus, rapidly generalized lymphopenia, preferential loss of Th17 population and T cell activation presented as characteristics of the early immune response in S-OIV-infected patients. These findings, therefore, may be helpful for an earlier diagnosis and further studies of immune pathogenesis of S-OIV infection.     

Comparison of activation marker and TCR V beta gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients.

Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) V beta gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-V beta MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the V beta repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of V beta families expressed by CD4+ or CD8+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more V beta families exhibited different distributions and these differences recurred among certain V beta segments, such as V beta 5.3 and V beta 21 in the CD4+ T cell population and V beta 5.2/5.3, V beta 12 and V beta 21 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.     

Mucosal T cell distribution during infection with respiratory syncytial virus.

Groups of 12-week-old Balb/c mice were inoculated intranasally with respiratory syncytial virus (RSV) and sacrificed at regular intervals after infection. T lymphocyte subset distribution was determined in lung tissue, bronchoalveolar lavage (BAL), peripheral blood, and spleen by means of flow cytometry employing monoclonal antibodies against the T cell membrane antigens Thy1.2 (pan-T), Ly2 (CD8), and L3T4 (CD4). Thy1.2+ cells increased in the lung from 35.4% of total lymphocytes before infection to 47.6% on day 7 after infection. This increase was largely accounted for by an increase in Ly2+ cells, which manifested a rise from 7.8% preinfection to 19.8% on day 7. The level of L3T4+ cells remained constant (27.9% preinfection vs. 25.2% on day 7). The L3T4+/Ly2+ ratio in the lungs reached a nadir 7 days post infection (1.5 vs. 3.5 before infection). The total cell count in BAL increased more than tenfold during the first week after infection. At the same time Thy1.2+ cells in the BAL increased from 41.1% of total lymphocytes on day 1 to 85.3% on day 7. Ly2+ influx was the most important (5.8% on day 1 vs. 41.1% on day 7). L3T4+ cell levels increased from 17.2% on day 1 to 40.1% on day 7. RSV-specific lymphocyte transformation was observed in BAL and blood but not in the lung tissue and spleen on day 7 postinfection. The disappearance of infectious virus in the lung correlated directly to the peak appearance of Ly2+ T cells in the lung tissue and BAL.     

Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus

T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(-/-)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(-/-) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-gamma (IFN-gamma) levels were similar in the lungs of IL-18(-/-) mice and wildtype mice. Intracellular IFN-gamma staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-gamma production is IL-18-independent during influenza virus infection. Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.     

A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.     

Respiratory syncytial virus infection among adults during influenza season: A frequently overlooked diagnosis

Our objective is to assess the characteristics of respiratory syncytial virus (RSV) infection in adult patients and to establish differences with influenza viruses. Fifty-four patients diagnosed with RSV and 198 with influenza were prospectively included. Compared with influenza, empirical antimicrobial therapy was more frequent in patients diagnosed with RSV, whereas antibiotic withdrawal at the time of diagnosis confirmation was lower (OR, 0.12; CI, 95% 0.01-0.90; P = 0.040). RSV-positive patients were more likely to need hospital readmission (OR, 3.00; CI, 95% 0.98-9.09; P = 0.053). The role of RSV infection in adults is often overlooked, leading to inappropriate use of antibiotics and a probable increase in nosocomial RSV transmission.