Age, the Thymus, and T Lymphocytes

Weinberg, Kenneth I.; Parkman, Robertson

doi:10.1056/nejm199501193320310

Cited by 31 publications

(13 citation statements)

References 10 publications

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“…35 The effects of high-dose chemotherapy and total-body irradiation on thymic function of the very young are largely unknown. 36 In the present study, we found that the ratio of CD4 ϩ cells to CD8 ϩ cells was normal in 90% of the infant recipients, but was inverted in half of the older pediatric patients. This result suggests that like adult recipients, many older children have a relatively reduced capacity to produce new CD4 ϩ lymphocytes after BMT; this reduction in capacity may be a possible secondary effect caused by the BMT-induced acceleration of the normal thymic aging process.…”

Section: Discussionmentioning

confidence: 64%

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Leung

Pitts

Burnette

et al. 2001

Bone Marrow Transplant

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Summary:The objective of this study is to investigate the outcome of children 24 months of age or younger (infants) at the time of allogeneic bone marrow transplantation (BMT) for acute leukemia or myelodysplasia. We analyzed the survival rate, prognostic factors, incidences of late sequelae, and immune reconstitution in 22 infants who underwent allogeneic BMT. The 5-year event-free survival estimate was 45.5% (95% confidence interval (CI), 24.4% to 63.3%). Six patients died of transplant-related complications and six died of disease relapse. Remission status at the time of BMT was the most important prognostic factor (P ‫؍‬ 0.005): no patient who received a transplant while their disease was not in remission survived, whereas the 5-year survival estimate for infants who underwent BMT during remission was 56% (95% CI, 31% to 75%). Long-term outcomes in the 10 infant survivors were compared with those of 10 older controls matched for diagnosis, disease status at the time of BMT, calendar year at the time of BMT, and source of stem cells. Immune function 1 year after transplantation and the incidences and spectra of late sequelae were similar for both groups during a median of 3.5 years (range, 1.5 to 7.2 years) of follow-up. Bone Marrow Transplantation (2001) 27, 717-722. Keywords: allogeneic transplantation; infant leukemia; myelodysplastic syndrome; late sequelaeThe incidences of lymphoid and myeloid leukemias in infants are approximately equal. Acute lymphoblastic leukemia (ALL) in infants accounts for 2.5% to 5% of all cases of childhood ALL, and acute myeloid leukemia (AML) in infants accounts for 6% to 14% of all cases of childhood AML. 1 The frequent presence of poor prognostic factors such as 11q23/MLL rearrangement in ALL and a high leukocyte count at the time of diagnosis of AML results in an overall long-term survival of only approxiCorrespondence: WH Leung,

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Section: Discussionmentioning

confidence: 64%

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Leung

Pitts

Burnette

et al. 2001

Bone Marrow Transplant

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“…These observations are consistent with clinical studies showing that, postmyeloablation, circulating naive CD4 ϩ and CD8 ϩ T cells are only found after relatively long periods of time (4-6 mo) and then usually in children and young adults (13)(14)(15)(16). Viewed in conjunction with a more extensive literature of thymic function in rodents (17)(18)(19)(20)(21)(22)(23), these data underscore the commonly-held belief (17,24,25) that the thymus is not present or not functional in adults.…”

Section: Introductionmentioning

confidence: 71%

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

McCune¹,

Loftus²,

Schmidt³

et al. 1998

J. Clin. Invest.

244

149

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The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive ( n ϭ 99) or HIV-1-seronegative ( n ϭ 32) subjects, and correlating these results with the level of circulating CD4 ϩ and CD8 ϩ T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4 ϩ T cell count ( P ϭ 0.02) and a higher percentage and absolute number of circulating naive (CD45RA ϩ CD62L ϩ ) CD4 ϩ T cells ( P Ͻ 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( Յ 39 yr) with CD4 counts in the range 300-500 cells/ l and in older subjects ( Ͼ 40 yr) regardless of CD4 count ( P ϭ 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease. ( J. Clin. Invest. 1998.

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“…8 However, there was no evidence in our study that infectious diseases were any more frequent among older patients. The physiological decline in immune function with age 8,[11][12][13][14] is reflected by lower CD4+ cell counts at inclusion in older patients in this study, as described by others. 23 This initial quantitative deficiency does not seem initially sufficient to explain the influence of age on disease progression.…”

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confidence: 99%

“…5 The pathophysiological phenomena underlying the influence of age are poorly known. Some authors explain it through the physiological decline in immune function, [11][12][13][14] which has been attributed to a quantitative 11 or qualitative 8 deficiency in CD4+ lymphocytes. One study has suggested that the influence of age on biological progression only emerges at a certain degree of immunodeficiency:…”

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confidence: 99%

Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: the SEROCO cohort (1988- 1994). The Seroco Study Group

Bélanger

Meyer²,

Carré³

et al. 1997

International Journal of Epidemiology

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Method. The influence of age at infection on progression of human immunodeficiency virus (HIV) disease to different clinical endpoints was studied among 393 HIV-seropositive adults selected from the French SEROCO cohort; follow-up lasted from January 1988 to November 1994. Selected patients had a known date of infection and were enrolled shortly after seroconversion. Age-associated risk ratios (RR) were estimated using the Cox model (age fitted as a continuous variable and RR expressed for each 10-year increment after adjustment for symptomatic primary infection and sexual preference). Results. Age had a weak influence on progression from the date of infection to the first category B event (crude RR = 1.15; adjusted RR = 1.09; 95% confidence interval [CI] : 0.89-1.36) but a marked influence on progression from the first category B to the first category C event (crude RR = 1.95; adjusted RR = 1.97; 95% CI : 1.37-2.79). Similar results were obtained after adjustment for the CD4 + cell count at enrolment. A qualitative CD4 + cell defect could explain the influence of age, but this remains to be confirmed. Conclusion. Age at infection should be included in the definition of CD4 + cell count thresholds for clinical management and treatment initiation. Risk factors for progression should be assessed according to the different clinical endpoints.

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Age, the Thymus, and T Lymphocytes

Cited by 31 publications

References 10 publications

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: the SEROCO cohort (1988- 1994). The Seroco Study Group

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