T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions

Friedrich, Wilhelm; O’Reilly, RJ; Koziner, Benjamín; Gebhard, David F.; Ra, Good; Rl, Evans

doi:10.1182/blood.v59.4.696.696

Cited by 102 publications

(12 citation statements)

References 16 publications

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“…In normal individuals most of the T-cells carry the helper T-cell marker (Reinherz et al 1980a, b). The inverted ratio between cytotoxic/sup-pressor and helper cell subsets in BMT patients has been reported to persist during acute GVHD (Friedrich et aL 1982, Atkinson et al 1982, Forman et al 1982, but the opposite has also been found (Reinherz et al 1979).…”

Section: Gvhd and Immunodeficiencymentioning

confidence: 98%

“…During the first months after BMT, several groups have shown that most of the T-cells in the peripheral blood belong to the subset carrying the same surface markers as cells with a cytotoxic/suppressor function (de Bruin et al 1981, Friedrich et al 1982, Atkinson et al 1982a, Forman et al 1982. This may be a reflection of the distribution of T-cell subsets in normal bone-marrow (Janossy et al 1981).…”

Section: Gvhd and Immunodeficiencymentioning

confidence: 99%

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Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Ringdén¹,

Persson²,

Johansson³

1983

Immunological Reviews

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IgE-levels are markedly elevated following bone-marrow transplantation in patients with and without GVHD. In patients with GVHD, there is a significant correlation between the timing of the IgE-increase and the appearance of clinical GVHD (p less than 0.01). The highest IgE-level (8000 kU/l) was noted in a recipient of a syngeneic graft. During the IgE-peak, the serum from this patient contained low concentrations of IgE reacting with several tested allergens as well as for the hapten TNP, which indicated polyclonal activation. In a patient with a known allergy to animal danders, RAST tests were positive against dog and cat both before and six weeks after total body irradiation and transplantation with marrow from a non-allergic donor. A slight increase in the amount of allergen-specific, IgE-antibodies was seen during the increase in total IgE. A non-allergic patient was transplanted with marrow from a donor allergic to timothy. Timothy-specific, IgE-antibodies were detected immediately after transplantation but they disappeared within a few days and could not be detected during the period of increase in total IgE. We believe that the IgE-elevation seen after conditioning with cytotoxic drugs and total body irradiation in BMT-patients is a polyclonal response in host B-cells induced during an acute, GVHR and influenced by disturbed regulatory T-cells. Lymphocytes from patients with acute GVHD had unusually large numbers of IgG/PFC in vitro after stimulation with staph. aureus Cowan 1 (p less than 0.001), which may reflect a clonal expansion of responsive B-cells.

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Section: Gvhd and Immunodeficiencymentioning

confidence: 98%

Section: Gvhd and Immunodeficiencymentioning

confidence: 99%

Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Ringdén¹,

Persson²,

Johansson³

1983

Immunological Reviews

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“…CD4+ lymphocytes are the major effector cells in cell-mediated immunity in TB and it has been shown that these cells in particular are low in numbers in proportion to CD8+ lymphocytes in BMT recipients with GVHD. 26 As a result they fail to provide helper activity as compared with CD4+ cells from healthy BMT recipients which constantly provide helper activity. 27 It is still controversial whether corticosteroid treatment is associated with the development of TB in BMT recipients.…”

Section: Epidemiologymentioning

confidence: 99%

Tuberculosis in blood and marrow transplant recipients

Yuen

Woo

2001

Hematological Oncology

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Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units. Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries. Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 10(5) inhabitants per year in Spain and about 100 cases per 10(5) inhabitants per year in Hong Kong respectively. The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7-57). The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients. Moreover, allogeneic transplantation, graft-versus-host disease, and total body irradiation were found to be risk factors associated with TB. Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11). On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100. The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non-infectious complications after BMT. As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months. In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted. The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored. With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV-infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients.

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“…The precise immunologic mechanism for GVHD is not known. Onset of GVHD has been associated with enhanced inversion of T-helper/T-suppressor cell ratios (19). The loss of T-helper function could account for diminished activation of residual host B lymphocytes and contribute to their disappearance.…”

Section: Discussionmentioning

confidence: 99%

Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO‐mismatched allogeneic bone marrow transplant recipient

Cockerill

Lyding

Zander

1989

European J of Haematology

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ABO‐mismatched bone marrow transplants have resulted in delayed red cell production in patients who have persistently elevated anti‐ABO isohemagglutinin titers. We present a patient with chronic myelogenous leukemia who received an HLA‐matched, ABO‐incompatible bone marrow transplant from his sister. Post‐transplant, he developed pure red cell aplasia with exuberant production of donor red cell precursors by in vitro BFU‐E assay. Restriction fragment length polymorphism (RFLP) analysis of bone marrow, peripheral blood and BFU‐E colonies demonstrated only donor type DNA post‐transplant. However, the patient had persistently elevated isohemagglutinin titer and Ph' chromosome‐positive metaphases on chromosome analysis, indicating the presence of persistent host lymphocytes. With onset of acute graft vs. host disease (GVHD), the isohemagglutinin titer dropped, Ph1 chromosome‐positive metaphases disappeared, and full hematopoietic recovery ensued. Longitudinal analysis of RFLP's, isohemagglutinin titers and chromosomes may be helpful in understanding the immunological interplay following allogeneic bone marrow transplantation.

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T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions

Cited by 102 publications

References 16 publications

Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Tuberculosis in blood and marrow transplant recipients

Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO‐mismatched allogeneic bone marrow transplant recipient

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