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Biomedical subjects

M T Roos

Publications and source records attributed to M T Roos.

At least 73 records · Page 4Linked to original sources
PubMed1992

Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection.

Nineteen individuals were studied for virologic and immunologic events during primary human immunodeficiency virus type 1 (HIV-1) infection. In 16 individuals only non-syncytium-inducing (NSI) isolates were detected; syncytium-inducing (SI) isolates were obtained from 3. Studies of transmitter-recipient pairs indicated that both NSI variants and SI variants were transmitted and that SI variants may be suppressed in the recipient. CD4+ T cells remained in the normal range in 15 of 16 individuals with NSI isolates but rapidly declined in all 3 individuals with SI variants, 1 of whom was treated with zidovudine. The most marked increase in CD8+ T cells and activated CD8+ T cells was observed in individuals with the most pronounced clinical signs of acute HIV-1 infection. Activated CD8+ T cells were only transiently elevated in individuals with SI variants, suggesting that an impaired cellular anti-HIV-1 immune response plays a role in the rapid progression to AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1992

Concordance of human immunodeficiency virus detection by polymerase chain reaction and by serologic assays in a Dutch cohort of seronegative homosexual men.

In three subgroups of a clinically and socially well defined group of Dutch homosexual men, the prevalence of human immunodeficiency virus type 1 (HIV-1) sequences in seronegative blood samples was studied using the polymerase chain reaction (PCR). In 19 seronegative partners of seropositive persons, no HIV-1 sequences were found by PCR in either early (1984/1985) or more recent (1987) samples. In 42 seronegative persons selected by their high risk for HIV-1 infection, none harbored HIV-1 sequences in either early (1985/1986) or late (1989) samples. In 15 people who seroconverted for HIV-1, only 2 samples collected 3 months before seroconversion were PCR-positive. These persons were also HIV antigen-positive at this time. These data suggest that a latent infection greater than 6 months does not occur and that the combination of HIV antibody and HIV antigen tests is appropriate and conclusive in most cases of HIV-1 infection.

Base Sequence↗
PubMed1992

Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype.

OBJECTIVE: To determine the kinetics of decline of CD4+ lymphocytes in HIV-1-infected asymptomatic homosexual men. METHODS: CD4+ lymphocytes were enumerated in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3-month intervals over 5 years. During follow-up, 45 men progressed to AIDS (excluding cases presenting with Kaposi's sarcoma). Correlation between rate of CD4+ cell decline and presence of a particular HIV-1 biological phenotype was analysed in 43 participants. RESULTS: CD4+ cell counts declined slowly and continuously in HIV-1-seropositive men who remained asymptomatic during follow-up. A biphasic CD4+ cell count decline was observed in the group who developed AIDS: the decline was slow and steady (5.6 x 10(6)/l per month, similar to that observed in the asymptomatic group) until 18 months before AIDS diagnosis, but became three to five times faster thereafter. Rapid CD4+ cell decline was significantly related to syncytium-inducing, fast-replicating HIV-1 isolates; during the period of slow and steady CD4+ cell count decline, non-syncytium-inducing isolates were predominant. CONCLUSIONS: At an average of 18 months preceding AIDS diagnosis, a three to fivefold increase in the rate of loss of CD4+ lymphocytes occurs, and may be related to the appearance of a more virulent HIV-1 phenotype.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Large diurnal variation in CD4 cell count and T-cell function among drug users: implications for clinical practice and epidemiological studies.

OBJECTIVE: To measure diurnal variation in the CD4 cell count and T-cell reactivity of drug users. DESIGN: A prospective epidemiological study among HIV-infected and non-infected drug users attending the Municipal Health Service of Amsterdam, The Netherlands. PATIENTS: Eleven HIV-infected and seven non-infected drug users. MAIN OUTCOME MEASURES: CD4 cell counts and T-cell reactivity three times a day. T-cell subsets and T-cell reactivity were determined from blinded samples within 2 hours. RESULTS: The number of CD4 cells increased by 130 x 10(6)/l (P < 0.05) in HIV-infected intravenous drug users over 8 hours. Following stimulation with anti-CD3 monoclonal antibodies, the T-cell reactivity of HIV-infected drug users rose from 118 to 221 c.p.m. (P < 0.01) over 8 hours. CD4 cell counts of the total study population increased by 37% and T-cell reactivity by 93%. The increase in the number of CD4 cells was more marked among active drug users than among drug users who had not used drugs recently. CONCLUSION: Variation in the CD4 cell count and in T-cell reactivity is large among drug users.

CD4-Positive T-Lymphocytes↗
PubMed1991

Frequent injecting impairs lymphocyte reactivity in HIV-positive and HIV-negative drug users.

To investigate whether drug use affected immunological parameters, we conducted a cross-sectional study of 321 drug users. Absolute numbers of CD4+ lymphocytes and the T-cell reactivity were lower in HIV-positive than in HIV-negative people. The functional capacity of the T-cell system as measured after stimulation with a monoclonal antibody directed against CD3 was found to be strongly associated with the frequency of injecting, while no relationship was found between the frequency of injecting and the total number of lymphocytes or T-cell subsets. HIV-negative and HIV-positive drug users who had injected a mean of three times a day in the preceding 4-6 months had a T-cell reactivity which was 40-50% lower compared with seronegative and with seropositive drug users who had not injected in the preceding months. We conclude that lymphocyte reactivity is depressed by frequent injecting in HIV-negative and HIV-positive drug users.

Adult↗
PubMed1991

Differences in clinical course in zidovudine-treated asymptomatic HIV-infected men associated with T-cell function at intake.

Declining CD4+ T-cell numbers and anti-CD3-induced T-cell responsiveness are prognostic markers for progression of HIV infection. We investigated the effect of long-term (2-year) zidovudine treatment on these immunological markers in a group of nine asymptomatic p24-antigenaemic men, five of whom progressed to AIDS. A group of 10 untreated HIV-infected men, five of whom progressed to AIDS, was studied as a control. At intake, 1 year before the start of treatment, CD4+ T-cell numbers in the groups were not significantly different. However, at that time progressors already exhibited an extremely low anti-CD3-induced T-cell responsiveness compared with non-progressors. In all people T-cell responsiveness and the number of CD4+ T-cells had improved 6 months after the start of zidovudine treatment. However, CD4+ T-cell numbers were not persistently elevated, and restoration of T-cell responsiveness was of only short duration. Our results show that zidovudine treatment in the asymptomatic phase of HIV infection did not result in a sustained improvement in T-cell function. Furthermore, they suggest that differences in clinical course among zidovudine-treated asymptomatics may be caused by heterogeneity of this group with respect to T-cell functional capacity at the start of treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Low T-cell responsiveness to activation via CD3/TCR is a prognostic marker for acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-1 (HIV-1)-infected men.

In a cohort of 300 HIV-1-infected homosexual men, studied longitudinally, the prognostic value of T-cell proliferative responses for development of AIDS was analyzed. In 15 persons we observed that, at seroconversion, T-cell reactivity to anti-CD3 monoclonal antibody (Mab) and phytohemagglutinin (PHA) was decreased to 20 and 60% of the normal values, respectively. After seroconversion, within 3 months, the response to anti-CD3 Mab and PHA returned to 60 and 80%, respectively, of the normal magnitude and declined thereafter. To investigate whether low T-cell reactivity correlated with progression to AIDS, groups of progressors and nonprogressors were compared. In individuals who progressed to AIDS, already 12 months before diagnosis, responses to anti-CD3 Mab were virtually absent, whereas at that time CD4+ cell numbers and reactivity to horse anti-human lymphocyte serum and PHA were still comparable to values observed for nonprogressors and the asymptomatic population as a whole. In a disease-free survival analysis, low anti-CD3 Mab reactivity predicted progression to AIDS. Our findings demonstrate that low T-cell responsiveness to anti-CD3 Mab is an early marker of progression toward AIDS in HIV-1 infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Whole-blood lymphocyte cultures.

A simple and reproducible method is described for the measurement of proliferative responses of peripheral blood lymphocytes in whole blood upon stimulation with horse anti-human lymphocyte serum (ALS), phytohaemagglutinin (PHA) or a monoclonal antibody (mAb) directed against CD3. Only small aliquots of blood are needed and separation procedures are not necessary. Since the method proved to be very reproducible and showed little variation, reference values of proliferation, expressed in cpm per 15 microliters blood and cpm per 10(3) CD3+ lymphocytes, were determined based upon the 5th and the 2.5th percentile of the distribution of the values in our reference population. In addition, the use of whole blood lymphocyte cultures in longitudinal studies of immunocompromised individuals is demonstrated.

Adolescent↗
PubMed1989

Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection.

The early effects of infection with human immunodeficiency virus (HIV) were investigated in homosexual men who had seroconverted for anti-HIV antibodies. Leukocyte functional activities were determined in longitudinally collected peripheral blood mononuclear cell samples. During the first 10 months following seroconversion, anti-CD3 monoclonal antibody-induced T cell proliferation, monocyte accessory function and T helper activity on B cell differentiation in a pokeweed mitogen-driven system were not affected. In contrast, from the moment of seroconversion on, B cells of seroconverted men failed to produce immunoglobulin in the pokeweed mitogen-driven system. This defect was not restored by addition of normal CD4+ T cells. Immunoglobulin synthesis induced by Staphylococcus aureus and interleukin 2 decreased gradually, until it was completely lost 10 months after seroconversion. In addition, proliferation in response to anti-IgM or Staphylococcus aureus by B cells from HIV seroconverted men was decreased. The lack of inducible in vitro B cell activity was not accompanied by elevated spontaneous Ig synthesis by B cells of the seroconverted men. In the second group of men studied during the 2nd year following seroconversion, T helper activity on normal B cell differentiation significantly decreased, whereas anti-CD3-induced T cell proliferation and monocyte accessory function were not significantly affected. Our results demonstrate that in almost all HIV-infected individuals B cell functional defects are the first leukocyte abnormalities observed preceding defects in T helper activity.

Antibody Formation↗
PubMed1989

Antibody response to a synthetic peptide covering a LAV-1/HTLV-IIIB neutralization epitope and disease progression.

Sequential sera of homosexual men participating in a prospective study on the incidence of HIV-1 infection and risk factors for AIDS were tested for the presence of antibodies to a synthetic 17-mer (Neu21; KSIRIQRGPGRAFVTIG) representing a neutralization epitope as present on the LAV-1/HTLV-IIIB strain of HIV-1. Of 191 at entry, 143 (75%) HIV-1-seropositive men remained anti-Neu21-negative during the follow-up period of 36 months. Thirty-seven (19%) HIV-1-seropositive men were persistently anti-Neu21-positive. Eleven (6%) HIV-1 seropositive men seroconverted for anti-Neu21 during follow-up. Of 75 men developing antibodies to HIV-1, 17 (23%) developed antibodies to Neu21. The incidence of anti-Neu21 seroconversion (calculated as attack rate) after 36 months was significantly lower (P less than 0.00001) among HIV-1-seropositive individuals (8%) than among the 75 HIV-1 seroconverters tested (25%), indicating that seroconversion to this neutralization domain occurs early during infection. AIDS and AIDS-related complex were diagnosed in 17% of the anti-Neu21 negatives and in 11% of the anti-Neu21 positives; this difference was not significant. The presence of HIV-1 antigen (29 versus 28%), the absence of antibodies to core proteins (45 versus 46%) and low CD4+ cell numbers (34 versus 40%) were not seen more frequently among anti-Neu21 negatives than among anti-Neu21 positives. These results argue against a role for antibodies to this LAV-1/HTLV-IIIB neutralization domain in protection against disease progression.

Adult↗
PubMed1989

Cellular and humoral immunity in various cohorts of male homosexuals in relation to infection with human immunodeficiency virus.

The relationship between infection with human immunodeficiency virus (HIV) and various immunological parameters was studied in: (a) healthy controls; (b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; (c) idem, but with anti-HIV antibodies; (d) patients with persistent generalized lymphadenopathy (PGL); (e) patients with AIDS-related syndrome; (f) patients with AIDS and opportunistic infections. In each group, consisting of 15-20 individuals, the following parameters were studied: absolute numbers of CD4+ and CD8+ cells; ratio CD4+/CD8+; cellular immune responses as measured in vivo by delayed-type hypersensitivity (DTH) and in vitro; and antibody response in vivo after immunization with a low dose of keyhole limpet haemocyanin. Healthy HIV antibody-positive individuals and patients with persistent generalized lymphadenopathy already showed a decreased CD4+/CD8+ ratio, mainly due to an increase in the number of CD8+ cells. The ratio in the AIDS-related syndrome and AIDS groups was even lower, but this was now due to low numbers of CD4+ cells while the number of CD8+ cells was normal. The lymphocyte proliferative response was low in the HIV antibody-positive group, normal in the group with persistent generalized lymphadenopathy and profoundly decreased in the AIDS-related syndrome and AIDS groups. DTH was enhanced in the PGL group and diminished in both ARC and AIDS. Compared to healthy controls, the antibody response upon immunization with a low dose of keyhole limpet haemocyanin was depressed (although not absent) in all groups studied, even in HIV antibody-negative homosexuals. In the HIV antibody-positive group, the severity of the impairment of the various parameters of immunocompetence was not related to the presence of HIV antigenaemia.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The role of interleukin-2 in proliferative responses in vitro of T cells from patients after bone marrow transplantation. Evidence that minor defects can lead to in vitro unresponsiveness.

We have studied lectin-induced interleukin-2 (IL-2) production and proliferation of peripheral blood mononuclear cells from patients who had undergone a successful allogeneic bone marrow transplantation. Shortly after transplantation, the T cells show a decreased proliferative response and a decreased IL-2 production. However, addition to the culture of exogenous IL-2 does not result in restoration of the proliferative response, which indicates that the low proliferative response is not due to decreased IL-2 production alone. Longitudinal studies show a substantial variation between patients in the time in which the capacity to produce IL-2 is restored; however, in all patients there is a period in which IL-2 production is still diminished, but the proliferative capacity, as measured upon addition of exogenous IL-2 to the culture, is almost within the normal range. Also during this period, the proliferative response of the T cells can be restored by the addition of irradiated "feeder cells" obtained from the bone-marrow donors, as these cells secrete IL-2 without consuming it. Because peripheral blood samples from patients after bone marrow transplantation show great imbalances in the distribution of T4/T8 subpopulations, we have studied the influence of an artificially produced "reverse T4/T8" ratio on the proliferative response to mitogen and (allos-)antigen stimulation of healthy donor T lymphocytes. Even at very low proportions of T4 cells, normal responses were obtained in the proliferation assays with polyclonal mitogens. Only the response to soluble antigens, such as tetanus toxoid, was impaired. However, a low proportion of T4 cells resulted in a low IL-2 production so that, when IL-2 is a limiting factor due to intrinsic defects of patient cells, an inverse T4/T8 ratio can cause a nonresponsiveness in in-vitro assays.

Bone Marrow Transplantation↗
PubMed1985

Immunoglobulin subclasses of antibodies to human T-cell leukemia/lymphoma virus I-associated antigens in acquired immune deficiency syndrome and lymphadenopathy syndrome.

Immunoglobulin G (IgG) and IgM antibodies to human T-cell leukemia/lymphoma virus-I (HTLV-I)-associated membrane antigens (HTLV-I-MA) were assayed by indirect cytospin immunofluorescence, and IgG and IgM antibodies to purified HTLV-I were assayed by enzyme-linked immunosorbent assay in sera from 119 immunologically well-characterized promiscuous male homosexuals in The Netherlands, of whom 9 suffered from acquired immune deficiency syndrome (AIDS), 18 suffered from lymphadenopathy syndrome (LAS), and 5 suffered from gay bowel syndrome. Antibodies to HTLV-I-MA were present in four of nine AIDS patients, including one patient with antibodies to purified HTLV-I. Antibodies to HTLV-I-MA were present in 6 of 18 LAS patients, including 3 patients with antibodies to purified HTLV-I. Of five patients with gay bowel syndrome, one had IgG and IgM antibodies to HTLV-I-MA. Of the four HTLV-I seropositive AIDS patients, two had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, one had only IgG antibodies, and one had only IgM antibodies. Of the six HTLV-I seropositive LAS patients, four had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, and two had only IgM antibodies. In the sera from 27 healthy homosexuals with and 60 without T-cell subset imbalances, no antibodies to HTLV-I or HTLV-I-MA were detected.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Bone marrow transplantation in man. Analysis of T and B cell functions in PWM driven Ig production.

The functional activity of B and T lymphocytes from the blood of eight patients, who had successfully been treated with allogeneic bone marrow for severe aplastic anaemia or acute leukaemia, was studied in pokeweed mitogen (PWM) driven polyclonal immunoglobulin synthesis. Activity of B cells was measured as IgM and IgG synthesis by a standard number (40 X 10(3] of patient lymphocytes in the presence or absence of healthy donor T cells. In addition, the frequency of PWM reactive B cells, giving rise to IgM and/or IgG producing daughter cells, was estimated by limiting dilution analysis. With this method, it was found that only a small percentage (1-3%) of peripheral blood B cells from healthy individuals is reactive to PWM. In the patients, both parameters for B cell reactivity were decreased during the first 40 weeks after bone marrow transplantation. As parameters for T cell activity, help and suppression on the Ig production by healthy donor lymphocytes were tested. In most patients, T helper cell activity was strongly decreased, whereas some patients had excessive T suppressor cell activity. The observed functional activities were only partially correlated with the marker profile of the T cell populations, as detected by reactivity with monoclonal antibodies. Each patient had a distinct, individual pattern of reconstitution of these functions. There was no positive correlation between Ig production in vitro and the capacity to form antibodies in vivo, nor between the other in vitro findings and clinical features, such as the occurrence of infections or graft versus host disease.

B-Lymphocytes↗
PubMed1981

Bone marrow transplantation in children with severe aplastic anemia: reconstitution of cellular immunity.

Cellular immune functions were evaluated longitudinally in seven children with severe aplastic anemia, who were successfully transplanted with bone marrow cells from an HLA-identical, mixed lymphocyte culture (MLC)-negative sibling. Several parameters were followed: the number of lymphocytes and E rosette-forming cells in the peripheral blood and the lymphocyte reactivity toward various mitogens, antigens, and allogeneic lymphocytes. Some patients already displayed decreased in vitro lymphocyte reactivity before transplantation, especially with regard to the response to pokeweed mitogen (PWM). After transplantation, a severe cellular immunodeficiency developed in all patients, with low numbers of T cells and markedly impaired responsiveness to mitogens, antigens, and allogeneic lymphocytes. Variations between patients were substantial, both with regard to the severity and duration of the immunodeficiency and to the pattern of the recovery of lymphocyte responses to mitogens and antigens. This variability might be attributable to an imbalanced proliferation of different lymphocyte subsets and/or the sequence of appearance of receptors for mitogens on the cell surface.

Anemia, Aplastic↗
PubMed1975

Antibody-dependent human lymphocytotoxicity: a micro assay system.

A micro assay system is described for measuring antibody-dependent lymphocytotoxicity with human effector cells. The target cells were mouse mastocytoma cells sensitized with rabbit antibody. The tests were performed in microtiter plates, each well containing 5 x 10(3) 51Cr-labeled target cells, together with varying numbers of effector cells. Whereas highly purified lymphocyte suspensions induced lysis, purified monocyte and granulocyte suspensions had virtually no effect. In parallel experiments it was shown that the latter cell suspensions were very active in lysing sensitized human erythrocytes, which in turn were not lysed by purified lymphocytes. Finally, it was shown that the lytic capacity of lymphocytes was not affected by preservation of the cells at liquid nitrogen temperature. It is concluded that the system described can be used for the clinical analysis of antibody-dependent lymphocytotoxicity in lymphocyte suspensions.

Animals↗