Diminished response to tick-borne encephalitis vaccination in thymectomized children

Prelog, Martina; Wilk, Cordula; Keller, Michael; Karall, Thomas; Orth, Dorothea; Geiger, Ralf; Walder, Gernot; Laufer, Guenther; Cottogni, M; Lothar, Bernd Zimmerhackl; Stein, Joerg; Grubeck‐Loebenstein, Beatrix; Wuerzner, R.

doi:10.1016/j.vaccine.2007.11.074

Cited by 37 publications

(25 citation statements)

References 39 publications

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“…Although all YATECs enrolled in the present study (including those with severe immunological alterations) were clinically asymptomatic, such phenotype is suggestive of a certain degree of immune fragility in this subgroup of YATECs. Of note, recent data suggest that thymectomized children present delayed antibody responses to tick-borne encephalitis vaccination (35). The demise of the thymus in the elderly is considered a major causative factor of declining immune competence (2,36).…”

Section: Discussionmentioning

confidence: 99%

Evidence of premature immune aging in patients thymectomized during early childhood

Sauce¹,

Larsen²,

et al. 2009

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While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4 + and CD8 + T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.

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Section: Discussionmentioning

confidence: 99%

Evidence of premature immune aging in patients thymectomized during early childhood

Sauce¹,

Larsen²,

et al. 2009

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“…Several studies have shown that in the first years after thymectomy at an early age, the composition of the T-cell compartment is dramatically affected. [14][15][16][17][18] The long-term effects of thymectomy at an early age are much less unequivocal, however, and aberrations in size and composition of represents scans with evidence of thymic tissue, but small for the age of the individual. F represents MRI scans with evidence of thymic tissue of similar size as healthy age-matched controls.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16][17][18] In pediatric cardiac surgery, thymectomy is performed to gain an unrestricted view of the operation site. Especially in neonates, in whom the thymus is relatively large, surgical procedures involving the large vessels necessitate complete removal of the thymus.…”

Section: Introductionmentioning

confidence: 99%

“…These changes in the T-cell pool at an early age occur without obvious clinical consequences, 14,19,20 although diminished responses to tick-borne encephalitis have been reported. 18 The long-term effects of thymectomy during early childhood on the composition of the T-cell compartment are less unequivocal. Whereas some thymectomized individuals show reduced total and naive CD4 ϩ and CD8 ϩ T-cell counts 15,21,22 and clear signs of premature immunosenescence 22 in the second and third decades of life, many other thymectomized individuals have peripheral T-cell pools comparable to those of age-matched healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration?

Gent¹,

Schadenberg²,

Otto³

et al. 2011

Blood

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Thymectomy during early childhood is generally thought to have serious consequences for the establishment of the Tcell compartment. In the present study, we investigated the composition of the T-cell pool in the first 3 decades after thymectomy during infancy due to cardiac surgery. In the first 5 years after thymectomy, naive and total CD4 ؉ and CD8 ؉ T-cell numbers in the blood and T-cell receptor excision circle (TREC) levels in CD4 ؉ T cells were significantly lower than in healthy age-matched controls. In the first years after thymectomy, plasma IL-7 levels were significantly elevated and peripheral T-cell proliferation levels were increased by ϳ 2-fold. From 5 years after thymectomy onward, naive CD4 ؉ and CD8 ؉ T-cell counts and TRECs were within the normal range. Because TREC levels are expected to decline continuously in the absence of thymic output, we investigated whether normalization of the naive T-cell pool could be due to regeneration of thymic tissue. In the majority of individuals who had been thymectomized during infancy, thymic tissue could indeed be identified on magnetic resonance imaging scans. Whereas thymectomy has severe effects on the establishment of the naive T-cell compartment during early childhood, our data suggest that functional regrowth of thymic tissue can limit its effects in subsequent years. (Blood. 2011;118(3):627-634)

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“…Moreover, naive CD4 + T cells had lower numbers of TCR rearrangement excision circles (TREC) and a higher expression of the proliferation marker Ki-67 [36], indicating increased homeostatic proliferation. Of clinical relevance, thymectomized patients had lower tick-borne encephalitis virus (TBEV)-specific IgG antibody titers after TBEV vaccination compared to healthy controls [38], demonstrating the importance of the thymus in maintaining the integrity of adaptive immunity throughout life.…”

Section: Age-related Alterations Of the Naive T Cell Compartmentmentioning

confidence: 99%

The Aging of the Adaptive Immune System

Herndler‐Brandstetter¹,

Weinberger²,

Pfister³

et al. 2011

CIR

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Adaptive immune responses are severely affected by the aging process as reflected by an increased morbidity and mortality from infectious diseases and a low efficacy of vaccination in elderly persons. Age-related changes within the bone marrow and thymus lead to an impaired generation of new T and B cells severely compromising the maintenance of a diverse and balanced T and B cell repertoire in old age. The maintenance of a balanced T cell repertoire is further challenged by latent persistent infections, such as Cytomegalovirus. Understanding the mechanisms of age-related alterations of the adaptive immune response may help to facilitate the development of more efficient vaccines for elderly persons and to envisage strategies to overcome immunosenescence.

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Diminished response to tick-borne encephalitis vaccination in thymectomized children

Cited by 37 publications

References 39 publications

Evidence of premature immune aging in patients thymectomized during early childhood

Evidence of premature immune aging in patients thymectomized during early childhood

Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration?

The Aging of the Adaptive Immune System

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