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Biomedical subjects

C R Rinaldo

Publications and source records attributed to C R Rinaldo.

At least 91 records · Page 5Linked to original sources
PubMed1990

Antibody-dependent cellular cytotoxicity mediated by CD16+ lymphocytes from HIV-seropositive homosexual men.

We investigated the ability of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-seropositive asymptomatic and mildly symptomatic homosexual men with known time of seroconversion to mediate antibody-dependent cellular cytotoxicity (ADCC) specific for HIV. PBMC from HIV-seronegative and -sero-positive subjects lysed T (CEM) cells persistently infected with HIV to a significantly greater degree than uninfected CEM cells in the presence of HIV antibody-positive serum in a 4-hr 51Cr release assay. The response was mediated by CD16+ cells. ADCC responses were lower in PBMC of 13 men tested 9 to 25 months (average, 16.1 months) after seroconversion to HIV as compared with seronegative subjects, and were further decreased in 11 men tested 26 to 38 months (average, 31.6 months) after seroconversion. Decreases in numbers of circulating CD16+ cells appeared to contribute to depression in ADCC activity. The suppressive effect of HIV infection on ADCC effector cell activity may be important in the immunopathogenesis of acquired immune deficiency syndrome.

Antibodies↗
PubMed1990

Cytotoxic activity against HIV-infected monocytes by recombinant interleukin 2-activated natural killer cells.

Natural killer (NK) cells have long been known to aid in the control of viral infections by killing virus-infected cells, including those infected with human immunodeficiency virus (HIV). Among the possible NK-susceptible target cells in an infected individual, the monocyte/macrophages are of special significance since they may serve as both a reservoir of HIV and aid in dissemination of the virus throughout the body. A new technique for the enrichment and cultivation of large numbers of recombinant interleukin 2 (rIL-2)-stimulated NK cells has been developed which provides cells with high cytotoxic activity. These IL-2-activated NK cells, adherent lymphokine-activated killer cells (A-LAK), can kill monocytes infected with HIV for 24 h to 7 days, with optimal target sensitivity between 3 and 7 days. Recognition and killing of the infected monocytes did not appear to be restricted by the major histocompatibility complex (MHC) antigens and could be cold-target inhibited by tumor cell lines. A-LAK cells may be useful in newer therapeutic approaches to treatment of HIV infection.

Cytotoxicity, Immunologic↗
PubMed1990

Possible beneficial effects of neutralizing antibodies and antibody-dependent, cell-mediated cytotoxicity in human immunodeficiency virus infection.

We studied the relationship between early human immunodeficiency virus type 1 (HIV-1) specific immune responses and pathogenesis of infection in participants enrolled in the multicenter AIDS cohort study (MACS). Sera collected at 6-month intervals for 2 years (visit 1-5) from 39 persons who seroconverted by enzyme-linked immunosorbent assay (ELISA) 6 months (visit 2) after enrollment were examined for isotype-specific Western blot reactivity, neutralizing antibodies (NA) against two divergent strains of HIV-1 (HIV-1IIIB and HIV-1RF), and for antibodies capable of participating in antibody-dependent, cell-mediated cytotoxicity (ADCC). These results were compared with changes in CD4+ cell number and episodes of lymphadenopathy. Twenty-five subjects had antibodies of at least one isotype reactive to at least one HIV-1 protein by Western blot at visit 1, before they became ELISA positive. NA reactive with HIV-1IIIB were detected before those reactive with HIV-1RF. NA were first observed in 11 sera at visit 2, in 22 sera at visit 3, and in 3 sera at visit 4; sera from three patients remained nonneutralizing through visit 5. In most cases, NA were detected after a decline in CD4+ cell numbers. The data are consistent with the interpretation that NA develop after about 16 to 18 months of declining CD4+ cell numbers, following which the rate of decline in CD4+ cell numbers slows. In contrast, HIV-1 envelope antigen-specific ADCC responses were first observed in 11 subjects at visit 1 when all 39 were NA and ELISA negative, in 12 subjects at visit 2, in 13 subjects at visit 3, and 1 subject at visit 4. Early ADCC responses were associated with high mean % CD4+ cell numbers and absence of lymphadenopathy throughout the 2-year observation period. Not all subjects who developed ADCC developed NA. In some subjects, ADCC and NA were detectable for the first time at the same visit, for others ADCC was detectable prior to NA, and for a few NA was detectable prior to ADCC. These findings suggest that ADCC and neutralization are mediated by different antibody populations, that they may partially inhibit the progress of HIV-1 infection, and that the late appearance of NA may relate to the failure of immunity to effect recovery from this infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Immune suppression by herpesviruses.

A unifying theme among the herpesviruses is the intimate interrelationship of virus infection with host cellular immune competence. Herpesviruses suppress cellular immunity. Recent advances suggest mechanisms of herpesvirus-induced immunosuppression that include inhibition of cytokine production and direct interaction of virus with major histocompatibility complex (MHC) components. This suppression appears to be of clinical significance primarily in patients with underlying immune deficiencies.

Cytomegalovirus Infections↗
PubMed1990

The effect of fresh lymphocytes on increased sensitivity of HIV-1 isolation: a multicenter study.

A multicenter study was undertaken to determine the sensitivity and reproducibility of markers for human immunodeficiency virus type 1 (HIV-1) viral growth and the effect of various preparations of lymphocytes on the sensitivity of standard and routinely used procedures for HIV-1 isolation. In phase 1, cocultivated culture supernatants obtained from 10 HIV-1 cultures were transported to three Multicenter AIDS Cohort Study (MACS) Virology Laboratories. Three commercial HIV-p24 antigen capture (AC) tests and two reverse transcriptase (RT) assays were used to ascertain the replication of HIV-1. The Du Pont and Abbott AC assays were found to be most sensitive (85-100%), and the RT assay with 24-h incubation period had comparable sensitivity (75-100%). In phase II, the sensitivity of standard cocultivation procedure for HIV-1 isolation was compared using freshly phytohemagglutinin-P (PHA-P)-stimulated, stimulated-frozen, and frozen-thawed and then stimulated normal human peripheral blood mononuclear cells (PBMCs) as cocultivating cells. Blood samples from 13 HIV-1 infected individuals with various CD4+ cell counts were cocultivated in each of the three MACS laboratories using one of the aforementioned normal PBMCs. The PHA-P-stimulated fresh normal PBMC showed a maximum isolation rate of 100% (13 of 13) with an average of 8 days to positivity. This rate of isolation was significantly greater than other rates using any one of the other PBMC preparations. These findings demonstrated that the use of freshly PHA-P stimulated PBMCs maximized HIV-1 isolation from blood when a sensitive HIV-1 p24 AC assay or RT assay with overnight incubation is employed for the detection of HIV in culture supernatant.

Blood Preservation↗
PubMed1990

Relation of alpha and gamma interferon levels to development of AIDS in homosexual men.

Homosexual men who were human immunodeficiency virus (HIV) seropositive at enrollment into the Pittsburgh portion of the Multicenter AIDS Cohort Study had elevated titers of serum alpha and gamma interferon (IFN) within 24 months prior to development of AIDS. In contrast, subjects who developed AIDS relatively early after seroconversion to HIV during this study did not have increased levels of alpha or gamma IFN.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Natural killer cell responses in homosexual men with early HIV infection.

Natural killer (NK) cells may be of significance in host defense against viral infections. In the present study, NK cell function was examined in relation to different phases of human immunodeficiency virus (HIV) infection. Peripheral blood mononuclear cells were tested for NK cell activity using K562 cell targets in a 51Cr-release assay. NK cell responses of 26 HIV-seronegative homosexual men were not significantly different from those of 30 heterosexual controls. NK activity was significantly lower in cells from 32 homosexual men with documented, early-phase HIV infection (average of 14 months; range of 3-27 months) as compared with that of seronegative men. The NK cell response decreased with time, since men within the first year of infection (n = 15; average of 7.8 months; range of 3-12 months) had greater NK cell activity than did those with longer duration of infection (n = 17; average of 18.3 months; range of 13-27 months). The decrease in NK cell activity did not correlate with altered numbers of cells bearing CD16 (NK) markers in these subjects. NK cell-mediated lysis and cell numbers were most severely depressed in a separate group of HIV-seropositive men who had acquired immune deficiency syndrome (AIDS). In vitro treatment with alpha-interferon (alpha-IFN) significantly enhanced NK activity of effector cells obtained from men within the first year of HIV infection but not in those with longer-term infection. Our results indicate that NK cell function decreases over time within the first 2 years of HIV infection in homosexual men, and is lowest in HIV-seropositive men with overt AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

No association between herpes simplex virus type-2 seropositivity or anogenital lesions and HIV seroconversion among homosexual men.

Recent reports have suggested that HSV-2 infection and associated anogenital ulcerations represent an important risk factor for acquisition of HIV infection. Although this is an appealing biological hypothesis, inferences drawn for homosexual men, as well as other at-risk populations, must be made after careful consideration of methods to control for potential confounding data. This report utilized a nested case-control study in which 49 homosexual HIV seroconverters were compared to 49 homosexual seronegative men matched on the prior level of receptive anal intercourse. No differences were observed for prior HSV-2 infection, since 21/49 (43%) of matched HIV seronegative men were HSV-2 antibody positive and 21/49 (43%) of HIV seroconverters were HSV-2 antibody positive at the visit 6 months before HIV seroconversion (odds ratio of 1.0, 95% confidence limits of 0.3-2.9) Similar findings were also observed for prior HSV-1 infection. Both self-reported symptoms and physical exam findings suggestive of HSV infection were rare during the 12 months prior to seroconversion and not associated with HIV seroconversion. These data do not support HSV-2 as a risk factor for seroconversion to HIV among homosexual men studied. These results should not be generalized to heterosexual transmission of HIV, particularly in Africa, where both an increased prevalence of genital ulcerative diseases and different etiologies have been observed.

Adult↗
PubMed1990

Preventing HIV infection in gay and bisexual men: experimental evaluation of attitude change from two risk reduction interventions.

In the course of learning their HIV serostatus, gay and bisexual men participated in small discussion groups aimed at increasing their practice of safer sex. Small discussion groups were randomly assigned to receive one of two interventions: a lecture/discussion by a gay health educator, or an intervention that included the lecture/discussion followed by a small group process aimed at increasing social skills for safer sex and at increasing peer support for safer sex. Men completed questionnaires relating to their knowledge about HIV and AIDS, attitudes toward sexual behavior change, and self-reported sexual behavior. At second follow-up, one year post-intervention, men who had received skills training and peer support endorsed significantly stronger attitudes in favor of safer sex than did men receiving lecture/discussion only. In particular, skills training and peer support caused greater reduction of the value placed on ejaculation inside the partner, stronger endorsement of plans to use condoms, and greater reduction of negative attitudes about condoms, than did lecture/discussion only. These results are helpful to design interventions for men who continue to engage in riskful behavior.

Adolescent↗
PubMed1989

Human immunodeficiency virus type 1 (HIV-1) infection a median of 18 months before a diagnostic western blot. Evidence from a cohort of homosexual men.

STUDY OBJECTIVE: To study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, we used an in-vitro amplification technique to detect HIV-1 nucleic acid sequences in sequential aliquots of peripheral blood mononuclear cells from homosexual men enrolled in the Multicenter AIDS Cohort Study. DESIGN AND PATIENTS: Blinded, longitudinal study of 24 homosexual men who were positive for HIV-1 antibodies at a recent follow-up visit. MEASUREMENTS AND MAIN RESULTS: Coded clinical samples were evaluated using two enzyme-linked immunosorbent assays (whole virus and gp120-gp41 fragment), Western blot, a p24 antigen capture assay, virus cocultivation, and in-vitro amplification of conserved regions from the HIV-1 gag and env open-reading frames. In 20 of the 24 men an HIV-1 enzymatically amplified product was detected before HIV-1 antibody seroconversion: at 42 months before seroconversion in two cases; at 36 months in one case; at 30 months in one case; at 24 months in four cases; at 18 months in eight cases; at 12 months in one case; and at 6 months in three cases (median, 18 months). In the four other men, detection of an HIV-1 enzymatically amplified product was concurrent with confirmation of antibody seroconversion by Western blot. CONCLUSIONS: There is a long and variable interval between virus acquisition and a diagnostic serum antibody response, perhaps due to the prolonged, persistent infection characteristic of the lentiviruses (family Retroviridae).

AIDS Serodiagnosis↗
PubMed1989

HLA-restricted lysis of herpes simplex virus-infected monocytes and macrophages mediated by CD4+ and CD8+ T lymphocytes.

Freshly isolated human peripheral blood monocytes and in vitro monocyte-derived macrophages were infected with HSV type 1 and used as target cells in a cell-mediated cytotoxicity assay. PBMC from both HSV-immune and non-immune donors were stimulated in vitro for 5 days with UV-inactivated HSV Ag and used as effector cells. Effectors from HSV-immune donors mediated virus-specific lysis of both monocyte and macrophage targets, whereas effectors from non-immune donors failed to mediate target cell lysis. Mean virus-specific lysis of autologous monocytes was (8.5 +/- (+/- 2.0)%) compared to a threefold greater virus-specific lysis of autologous macrophages (24.7 (+/- 4.3)%). More than 70% of this lysis was mediated by CD16- T lymphocytes. Further analysis demonstrated that the majority of the lysis against autologous and allogeneic targets was HLA-DR-restricted and mediated by CD4+ CTL. However, CD8+ CTL also contributed to the lysis of autologous targets as well as allogeneic targets having a common HLA-A and/or -B determinant. The HLA-restricted cytotoxicity was virus-specific as HSV-infected, but not CMV-infected, cells were lysed. CTL-mediated lysis of HSV-infected monocytes and macrophages may be of significance in the anti-viral and immunoregulatory host response.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Biological response modifier enhances the activity of natural killer cell against human cytomegalovirus-infected cells.

Peripheral blood lymphocytes (PBL) from two human cytomegalovirus (CMV)-seronegative donors and eight CMV-seropositive donors were cultured for 3 days with or without the biological response modifier OK-432 and examined for lysis of K562 cells and CMV-infected MRC-5 cells. OK-432-stimulated PBL exhibited significantly greater natural killer (NK) activity than did unstimulated PBL. There was no difference in activity of NK cells in PBL prepared from CMV-seronegative and -seropositive donors. Antibody-complement depletion studies suggested that OK-432-stimulated NK activity was associated with Leu-7-positive cells. The ability of OK-432 to sustain the NK activity in PBL was decreased when the CD4-positive population of lymphocytes was eliminated by antibody-complement depletion prior to OK-432 stimulation. The ability of OK-432 to sustain the NK activity of PBL was also significantly decreased in the presence of monoclonal antibody against recombinant human interleukin-2. The results suggest that the activity of human NK cells against K562 and CMV-infected MRC-5 target cells can be sustained in vitro by OK-432-stimulated T-helper cells and that the effect of the T-helper cells is mediated, at least in part, by interleukin-2.

Adult↗
PubMed1989

Enhanced antibody responses to Epstein-Barr virus in HIV-infected homosexual men.

We investigated the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infections in 593 homosexual men. The status of EBV infection in this group was evaluated based on serological evidence of EBV-specific antibody responses. The geometric mean titers (GMT) of antibody to EBV capsid antigen (EBV-VCA) (1:154) and EBV early antigen (EA) (1:16) in 141 HIV-seropositive men were significantly higher than respective titers in 452 HIV seronegative men (1:95 and 1:12). Antibody titers to EBV were higher in HIV-infected men with lymphadenopathy than in asymptomatic HIV-seropositive men. However, these correlation were less evident in patients with AIDS-related complex. Elevated antibody titers to EBV were found to be independent of levels of total serum IgG. Cytomegalovirus (CMV) antibody titers were also found to be significantly increased among HIV-seropositive men, independent of total IgG. Antibody titers to EBV were not correlated with those to CMV in either HIV-seronegative or HIV-seropositive men. Subjects without evidence of HIV infection, but who had high antibody titers to EBV-VCA and EBV-EA, had elevated mean numbers of CD3+, CD4+, and CD8+ cells, and lower levels of CD4+/CD8+ cell ratios compared to subjects with low EBV-antibody titers. This study suggests that the elevated levels of circulating antibodies against EBV in homosexual men are associated with loss of control of latent EBV due to HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Factors related to seroconversion among homo- and bisexual men after attending a risk-reduction educational session.

Thirteen homosexual men, volunteers in a study of the natural history of HIV, who seroconverted to HIV after participating in an educational program on HIV prevention, were interviewed about the circumstances leading to their seroconversion. Six men had participated in unprotected anal intercourse with at least one partner whom they believed was HIV-negative. Four men attributed their conversion to mental health problems or to drug and alcohol use. Two men's seroconversions could not be ascertained and one man attributed seroconversion to a condom break. Most men who had learned how to avoid infection, and had successfully done so for a time, had knowingly engaged in unsafe behaviors because of strong emotional responses to certain partners or because of mental health or drug and alcohol-related problems. Skills training for dealing with partners who pressure men to behave unsafely is needed, as is mental health and drug and alcohol counseling for men at risk for HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986.

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV-1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P less than 0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1.

Blotting, Western↗
PubMed1989

Coevolution of virulent virus and resistant cells as a mechanism of persistence of herpes simplex virus type 1 in a human T lymphoblastoid cell line.

Infection of the lymphoblastoid CEM cell line with herpes simplex virus (HSV) type 1 results in a persistent infection with production of infectious virus. Evidence suggests that the persistent infection was not maintained by interferon or non-interferon-soluble antiviral inhibitors. Treatment of persistently infected cells with anti-HSV serum (termed CEMACR cells) or elevated temperature (39 degrees C) for 14 days (termed CEMTCR cells) resulted in loss of evidence of virus. HSV DNA was not detected in CEMACR or CEMTCR cells by Southern blot or in situ hybridization. The CEMACR or CEMTCR cells, however, were resistant to reinfection with homologous, parental virus (HSV0), but were susceptible to heterologous virus (vesicular stomatitis virus). Resistance to reinfection with HSV was not absolute; CEMACR or CEMTCR cells were less permissive to virus isolated from persistently infected cultures at times early in the course of infection, but were more permissive for HSV isolated at later times. Virus isolated later during persistent infection also displayed progressively increased virulence for the parental CEM cells. These results suggest that persistent infection of a human T lymphoblastoid cell line, CEM, with HSV-1 is maintained by a genetically determined cell-virus equilibrium, in which the resistance of cells and virulence of virus increase during persistence.

Animals↗
PubMed1989

Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus.

Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and -seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin-2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities.

Acquired Immunodeficiency Syndrome↗