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Biomedical subjects

J C Gea-Banacloche

Publications and source records attributed to J C Gea-Banacloche.

18 recordsLinked to original sources
PubMed2000

Longitudinal changes in CD4+ T cell antigen receptor diversity and naive/memory cell phenotype during 9 to 26 months of antiretroviral therapy of HIV-infected patients.

Although skewing of the CD4+ TCR repertoire in advanced HIV infection is well documented, increases in polyclonality during antiretroviral therapy have been less consistently observed. Ten patients, each with documented abnormalities within the CD4+ TCR repertoire, were studied by CDR3 spectratyping, semiquantitative PCR, and SSCP during 9-26 months of therapy. Naive and memory cell phenotypes were analyzed by flow cytometry. Six of 10 patients showed increased polyclonality of their TCR repertoires, 1 showed no change, and 3 showed increased TCR skewing, despite suppressed viral replication. Overall, there was no significant change in the percentage of abnormal BV subfamilies (from a mean of 25.5 to 17.1%) or the percentage of naive CD4+ T cells (from a mean of 18 to 25%). Further, progression of TCR repertoire disruptions was observed in some patients even with suppression of plasma viral RNA below 500 copies/ml. Although a spectrum of changes may be seen within the CD4+ TCR repertoire in the setting of antiretroviral therapy, increases in polyclonality are observed in some patients.

Anti-HIV Agents↗
PubMed2000

Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors.

The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.

Adult↗
PubMed2000

Resistance to replication of human immunodeficiency virus challenge in SCID-Hu mice engrafted with peripheral blood mononuclear cells of nonprogressors is mediated by CD8(+) T cells and associated with a proliferative response to p24 antigen.

High levels of resistance to challenge with human immunodeficiency virus type 1 SF162 were observed in animals engrafted with peripheral blood mononuclear cells of four long-term nonprogressors (LTNPs). Resistance was abrogated by depletion of CD8(+) T cells in vivo and was observed only in LTNPs with proliferative responses to p24. In a subgroup of nonprogressors, CD8(+) T cells mediated restriction of challenge viruses, and this response was associated with strong proliferative responses to p24 antigen.

Animals↗
PubMed1999

Immune reconstitution in HIV infection.

The weight of the published evidence suggest that there is clinically significant immune recovery in a sizable fraction of HIV-infected patients who achieve suppression of viral replication. At the same time, it is clear that very few patients regain normal (i.e. equivalent to pre-infection) immune function, at least after the follow-up periods available so far. The experience from bone-marrow transplantation or intensive chemotherapy in adults suggests that such kind of immune reconstitution is unlikely (at least with treatments limited to stopping virus replication) once the immune system has been sufficiently damaged. It is also clear that effective immunity to HIV is not achieved in a significant proportion of patients. These findings have implications for both basic research and clinical practice. From the laboratory perspective, besides the urgent need to characterize the protective immunity to HIV (if it exists), it would be desirable to find some simple measure of the immune function of patients who receive therapy. The combination of markers of immune activation together with CD4 cell count and viral load should be further evaluated in this context. Regarding clinical practice, it is likely that prophylaxes for opportunistic infections can be discontinued uneventfully in the majority of patients responding to HAART. Although the evidence is not yet conclusive, all available data suggest this will be the case. Given that there is significant immune reconstitution even in advanced disease, it is tempting to consider if this fact can be used to support antiviral therapy recommendations that are less aggressive than the current ones. HIV eradication by pharmacologic means alone does not seem possible yet, and no effective immune response to HIV seems to be generated by starting therapy in the asymptomatic (as opposed to acute infection) stage of the disease. At the same time, the follow-up studies on prolonged antiretroviral therapy suggest that virologic failure will take place despite many months of seemingly adequate suppression. This fact, taken together with the side effects and inconvience of current antiretroviral regimens, can be used to support an argument in favor of evaluating strategies to treat later rather than earlier.

CD4-Positive T-Lymphocytes↗
PubMed1998

Progression of human immunodeficiency virus disease is associated with increasing disruptions within the CD4+ T cell receptor repertoire.

The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.

CD4 Lymphocyte Count↗
PubMed1997

Deficiency of naive T cells in patients with sudden deafness.

BACKGROUND: Although there are a number of reports concerned with the role of immunity in the sudden onset of progressive sensorineural hearing loss, there are few references dealing with the involvement of immune-mediated mechanisms in sudden deafness. OBJECTIVES: To study the phenotype of peripheral blood lymphocytes in a group of patients with sudden deafness by use of 3-color flow cytometry. DESIGN: The study was carried out prior to the start of steroid therapy. Fourteen patients underwent a follow-up study once steroid therapy had been completed. Prospective analysis, case-control. SETTING: Tertiary case referral center, ambulatory and hospitalized care. PATIENTS: Twenty-two patients (13 men and 9 women; mean age, 45.3 years) were compared with 14 healthy control subjects (9 men and 5 women; mean age, 36 years). Patients were divided in 2 groups according to their response to steroid therapy. RESULTS: Decreased numbers of both CD4+ helper cells (38.4% vs 45.5%; P = .04) and CD8+ cytotoxic cells (17.5% vs 22.3%; P = .02) were observed in patients and compared with those in the control subjects, as well as reduced numbers of CD4+CD45RA+ cells (14.4% vs 29.3%; P = .01) and CD8+CD45RA+ naive cells (18.2% vs 25.4%; P = .04). In the group of patients with a good response to steroid therapy (group 1), a tendency toward normalization of the CD4+ (pretreatment, 38.6%; posttreatment, 44.6%), CD4+CD45RA+ (pretreatment, 15.2%; posttreatment, 21.7%), and CD4+CD45RO+ (pretreatment, 21.1%; posttreatment, 18.2%) cell counts was observed, with a slight decrease in the CD8+ population (pretreatment, 18%; posttreatment, 15.7%). However, in patients with a poorer response (group 2), while there were increases in the CD4+ (pretreatment, 38%, posttreatment, 50%) and CD4+CD45RA+ (pretreatment, 12.8%; posttreatment, 16.7%) cell counts after steroid therapy, there was a significant increment in the CD4+CD45RO+ memory cell count (pretreatment, 14.1%; posttreatment, 28.5%) and low CD8+CD45RA+ counts (pretreatment, 14.6%; posttreatment, 15.5%). No differences were observed in the numbers of B or natural killer cells or in the presence of activation antigens CD25 and HLA-DR when pretreatment and posttreatment levels were compared. CONCLUSION: These results demonstrate significant abnormalities in the subpopulations of lymphocytes in patients with sudden hearing loss, suggesting the existence of immune-mediated responses in the inner ear as possible etiopathogenic factors in this entity.

Adolescent↗
PubMed1997

HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies.

Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+ T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.

CD4-Positive T-Lymphocytes↗
PubMed1997

Induction of apoptosis by 2-chlorodeoxyadenosine in B cell chronic lymphocytic leukemia.

We investigated whether 2-chlorodexoyadenosine could induce apoptosis in B cell chronic lymphocytic leukemia (B-CLL) cells in vitro using clinically achievable drug doses, measuring apoptosis ratio by flow cytometry. B cells were isolated from previously untreated patients and apoptosis was measured in these cells immediately after isolation and following incubation in vitro, without and with 2-chlorodeoxyadenosine at different concentrations, for 24 and 48 h. Distribution of cellular DNA content and quantitative analysis of apoptosis were determined by standard propidium iodide staining and flow cytometry. Spontaneous apoptosis occurred in B-CLL cells incubated in vitro in the absence of drug, but the level of apoptosis was greater in cells treated with 2-chlorodeoxyadenosine after the second day of culture. The present in vitro study of B-CLL cells from previously untreated patients suggests this chemotherapeutic agent activates a program of cell death by apoptosis using a drug dose equivalent to the physiological concentration used in patients in vivo. These data reveal an interesting possibility in the 2-chlorodeoxyadenosine treatment of untreated patients by neoplastic B cell apoptosis induction.

Adult↗
PubMed1996

Natural killer cell proliferation and renal disease: a functional and phenotypic study.

We describe a 57-year-old woman who presented with a constitutional syndrome, glomerulonephritis, and lymphocytosis. The phenotypic study, using flow cytometry, showed an expansion of natural killer (NK) cells (CD2+, CD3-, CD16+, CD56+, and CD7+). We performed a functional study of peripheral blood mononuclear cells (PBMCs) and of purified CD16+ cells (NK cells) and CD3+ cells (normal T cells). The expanded NK cell population, CD16+, did not proliferate with phytohemagglutinin (PHA) or anti-CD3 but showed a dose-dependent proliferation with recombinant interleukin-2 (rIL-2) and also proliferated with phorbol dibutyrate. This population showed very strong NK and lymphokine-activated killer cell (LAK) activities. The patient's symptoms resolved spontaneously without treatment. Three years later, however, there is still abnormal renal function, and the expansion of NK cells persists, although with no indication of malignancy. We review the features of the different large granular lymphocyte proliferations and their seldom described relationship with renal disease.

Antigens, CD↗
PubMed1995

Natural killer cell activity in patients with pernicious anemia.

Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma that ranges from three- to fivefold greater than that of the general population. It has been reported that NK cells may be involved in immunosurveillance against tumor spread. The natural killer cell activity of peripheral blood mononuclear cells was analyzed in 22 patients with pernicious anemia and in 19 healthy controls. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of gastrin levels and time elapsed since diagnosis. According to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+) were found in peripheral blood mononuclear cells from patients and healthy controls. Our results show that in pernicious anemia patients, the percentage of NK cells present in peripheral blood mononuclear cells and their lytic activity are normal.

Aged↗
PubMed1994

Functional and phenotypic analysis of T-lymphocytes in laryngeal carcinoma.

We studied the functional response and phenotypic characterization of peripheral blood T cells and their correlation with the clinical stage of disease in 29 males with previously untreated carcinoma of the larynx and 24 healthy male controls. Peripheral blood T cells, phenotypically CD2+ CD3+, were significantly decreased in the patients relative to the controls. Patients with advanced locoregional extension (T4 and N1, 2, 3) also showed a diminution of the CD4+ subpopulation of T cells. DNA synthesis by purified T cells showed similar blastogenic responses in patients and controls; the interleukin-2 production of phytohemagglutinin stimulated lymphocytes was also normal. We conclude that in patients with laryngeal carcinoma there is a phenotypic alteration of the T cells that is variable according to tumor stage, without functional alterations in blastogenic capacity or IL-2 production.

Adult↗
PubMed1993

Natural killer cell activity in laryngeal carcinoma.

We studied the relationship of natural killer cell activity from peripheral blood mononuclear cells with the clinical and pathologic stage of disease in 23 male patients with previously untreated carcinoma of the larynx and 22 healthy male control subjects. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of stage, tumor size, and clinical cervical adenopathies. Natural killer cell activity, however, was significantly decreased in patients with pathologic cervical lymph node involvement. The number of natural killer cells, as estimated by CD16 and CD56 monoclonal antibodies, was similar in all groups of subjects. We conclude that in patients with laryngeal carcinoma, there is a correlation between deficient natural killer cell activity and nodal metastases, which may represent a prognostic indicator in these patients.

Adult↗
PubMedDate not supplied

[Study of spontaneous cytotoxic activity in laryngeal carcinoma: prognostic value].

The status of natural killer (NK) cell activity in peripheral blood, based on number and functional state, was studied in relation to the clinical and histopathologic stage of 52 patients with laryngeal carcinoma and in 23 healthy controls. The number of NK cells, estimated using CD16 and CD56 monoclonal antibodies, was similar in patients and controls and showed no relation to tumor size and nodal involvement. NK cell function did not show significant differences in spontaneous cytotoxic activity either overall or in relation to tumor size and the presence of palpable lymph nodes. However, cytotoxic activity was significantly lower in patients who had histologically confirmed nodal involvement. NK activity under 36% (the percentage of specific lysis at an effector:target dilution of 50:1) was suggested the probable presence of nodal metastases and was a highly sensitive and specific test. In patients with laryngeal carcinoma, NK-cell cytotoxic activity may be an independent prognostic parameter for evaluating cervical lymph node involvement.

Adult↗