Detection of microbial antigenic components of circulating immune complexes in HIV patients:Involvement in CD4^+ T lymphocyte count depletion

Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of 100 HIV sero-positive and 100 HIV sero-negative participants.These were categorized into 3 grades based on CD4 count:】 500 cell/mm,200-499 cell/mm3 and 【200 cell/mm3.The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3 Germany.Results:Antigenic component of immune complexes of various infectious agents was detected in 99 and 70 HIV seropositive and HIV sero-negative participants,respectively.In group A,there were 10 HIV positive participants,including 4(40.0%) had circulating immune complexes(CICs) due to Salmonella species only:1(10.0%) due to Salmonella-Plasmodium falciparum(P.falciparum),SalmonellaP. falciparum-HCV and P.falciparum antigens,respectively.In group B,45(45.4%) HIV seropositive participants with CICs had CD4 T lymphocyte count between 200-499 cells/mm^3.Out of these,20(44.4%) had CICs due to Salmonella species only:9(20%) due to Salmonella-P. falciparum.In group C,there were 44(44.4%) HIV sero-positive participants,including 3(6.8%) due to Salmonella species only:24(54.4%) due to Salmonella-P.falciparum:2(4.5%) due to P. falciparum only.Conclusions:In HIV sero-positive participants,presence of heterogeneity of Salmonella species-P.falciparum antigens was highly incriminated in CD4 count depletion but not homogeneity of malaria parasites antigens.Malaria parasites antigens only were incriminated in CD4^+ count depletion amongst HIV sero-negative participants.Before taking any decision on the management of HIV-1-positive individuals,their malaria and Salmonella paratyphi status should be assessed,but not malaria status alone.

Community Normal Reference Values for CD3+, CD4+, CD8+T Lymphocytes and Leucocytes among Immunocompetent Adults in Coastal Kenya

Background: Studies on the reference values of CD4 and CD3 T cells in healthy individuals have continued to gain significance because of the importance of these immunological markers in the initiation of antiretroviral therapy and prophylactic drugs for opportunistic infections. These ranges tend to vary across populations. The CD4:CD8 ratio is used to measure of how balanced immune function is. Therefore, this study aimed at determining normal reference values for CD4+ and CD3+T-lymphocytes and leucocytes in healthy adults in Coastal Kenya. Methods: A cross-sectional study was carried between May 2015 and February 2016 in Coast General Referral hospital, Tudor, Port-Reitz, Mlaleo, Likoni and Sub-County hospitals. Participants were recruited from voluntary HIV counselling and testing clinics. Patients were counselled for HIV test and those who consented were tested for HIV. They were screened for diseases that potentially cause lymphocyte homeostasis perturbation. CD4+, CD3+ CD8+cells/μl were analyzed using a BD FACSCount flow cytometer (Becton-Dickson, NJ). Results: We enrolled 500 participants, two hundred and forty (48.0%) were males and two hundred and sixty (52.0) females. The mean CD4 cell count was 1054.9 ± 95% CI 1041.2 - 1068.6 cells/mm3, absolute CD8 was 688.4 ± 95% CI 679.1 - 697.7 cells/mm3, absolute CD3 cell count was 1945.1 ± 95% CI 1907.4 - 1982.2 cells/mm3 absolute leukocyte count 5.19 ± 95% CI 5.12 - 5.19, absolute lymphocyte count 1.85 ± 95% CI1.83 - 1.88 and haemoglobin level 12.76 ± 95% CI 12.65 - 12.87. Females had significantly higher mean CD4 and CD8 T cell counts than males (p < 0.05). The mean values of white blood cells 4.7 (3.0 - 7.9) × 109/l, platelets 239 (77 - 353) × 109/l and erythrocytes 4.65 (3.51 - 5.40) × 109 were significantly higher in males than females (p Conclusion: Immunohaematological markers found in this study were different from the standard values for the western countries. Females had significantly higher mean CD4+T and CD3+T cell counts but lower mean haemoglobin level, erythrocytes, white blood cells and platelets than males. Our findings provide new insight in the CD4 and CD3 T cell reference values of Kenyans.

Impact of baseline CD4^＋ T cell counts on the efficacy of nevirapinebased highly active antiretroviral therapy in Chinese HIV/AIDS patients： a prospective, multicentric study

Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）. Whether and how the baseline CD4^＋T cell count affects the immunological and viral responses or adverse reactions to nevirapine （NVP）-containing HAART in Chinese HIV-1 infected adults remain to be characterized. Methods One hundred and ninety-eight HIV-seropositive antiretroviral therapy （ART）-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4^＋T cell counts either between 100-200 cells/μl or 201-350 cells/μl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. Results Eighty-six and 112 subjects ranged their CD4^＋T cell counts 100-200 cells/μl and 201-350 cells/μl, respectively. The pre-HAART viral load in CD4 201-350 cells/μl group was significantly lower than that in CD4 100-200 cells/μl group （P=0.000）. After treatment, no significant differences were observed between these two groups either in the plasma viral load （pVL） or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4^＋T cell counts were statistically higher in the 201-350 group during the entire follow-ups （P 〈0.01） though CD4^＋ T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4^＋ T cell counts were increased to 331 cells/μl for CD4 100-200 cells/μl group and to 462 cells/μl for CD4 201-350 cells/μl group. Only a slightly higher incidence of nausea was observed in CD4 201-350 cells/μl group （P=0.05） among all adverse reactions, including rash and liver function abnormality. Conclusions The pVLs and viral response rates are unlikely to be associated with the baseline CD4^＋T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4^＋T cell counts could result in higher total CD4^＋T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/μl.

Biological features of intrahepatic CD4^(+)CD25^(+)T cells in the naturally tolerance of rat liver transplantation

The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplan-tation was performed in two allogeneic rat strain combina-tions,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients[Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DA-to-DA].The proportion of intrahepatic CD4^(+)CD25^(+)T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4^(+)CD25^(+)T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4^(+)CD25^(-)T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The pro-portion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tole-rance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4^(+)CD25^(+)T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4^(+)CD25^(+)Tcells sorted by MACS was 86%–93%.The CD4^(+)CD25^(+)T cells could specifically express the Foxp3 gene compared with CD4^(+)CD25^(-)T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4^(+)CD25^(+)T cells more obviously than the syngegnic spleen cells.CD4^(+)CD25^(+)Tr cells could suppress the proliferation of CD4^(+)CD25^(-)T cells,but the inhibition was reversed by exo-genous IL-2(200 U/mL).The CD4^(+)CD25^(+)T regulatory cells specifically express the Foxp3 gene,which may play animpor-tant role in the induction of liver transplantation tolerance by suppressing the reaction of effective T cells.

SATURATION EFFECTS FOR CTL MEDIATED CONTROL OF HIV-1 INFECTION： A MATHEMATICAL STUDY

The relations between the Human Immunodeficiency Virus-1 （HIV-1） and the human immune system are astonishingly multifaceted, where the critical role for cytotoxic T lymphocytes （CTLs） in the suppression of viral replication in HIV-1 infected individuals cannot be ignored. In this research paper, we have proposed a mathematical model incorporating half saturation constant through the CTL mediated killing process and also in that sense, it has been infiltrated in the generation process of CTL through infected cells. To make the model more realistic, a time lag is introduced in the generation term of CTL population. Also an optimal control theory paradigm is used in our mathematical model to suppress the viral production. From our entire analysis, we have found threshold condition of half saturation constant and treatment schedule so that we can handle the situation of Acquired Immunodeficiency Syndrome （AIDS） patients in a better way. Our analysis reveals that, if the half saturation constant is around 47 mm^-3 in the saturation process and the drug therapy is to be used around 76 days, then we can get adequate results for better treatment of a HIV-1 patient. Based on numerical results, we observed that in a highly unstable situation, administration of chemotherapy at a high dose can stabilize the system.