Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia

Abstract Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand pre-existing memory T cells. (Blood. 2005; 106:1749-1754)

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CD4 + T‐cell memory: generation and multi‐faceted roles for CD4 + T cells in protective immunity to influenza

Immunological Reviews ◽

10.1111/j.0105-2896.2006.00388.x ◽

2006 ◽

Vol 211 (1) ◽

pp. 8-22 ◽

Cited By ~ 131

Author(s):

Susan L. Swain ◽

Javed N. Agrewala ◽

Deborah M. Brown ◽

Dawn M. Jelley‐Gibbs ◽

Susanne Golech ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Protective Immunity ◽

Cd4 T Cell ◽

T Cell Memory ◽

Cell Memory

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Protection against immunopathological consequences of a viral infection by activated but not resting cytotoxic T cells: T cell memory without "memory T cells"?

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.94.2.640 ◽

1997 ◽

Vol 94 (2) ◽

pp. 640-645 ◽

Cited By ~ 95

Author(s):

M. F. Bachmann ◽

T. M. Kundig ◽

H. Hengartner ◽

R. M. Zinkernagel

Keyword(s):

T Cells ◽

T Cell ◽

Viral Infection ◽

Memory T Cells ◽

Cytotoxic T Cells ◽

T Cell Memory ◽

Cell Memory

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Profound Protection against Respiratory Challenge with a Lethal H7N7 Influenza A Virus by Increasing the Magnitude of CD8+ T-Cell Memory

Journal of Virology ◽

10.1128/jvi.74.24.11690-11696.2000 ◽

2000 ◽

Vol 74 (24) ◽

pp. 11690-11696 ◽

Cited By ~ 94

Author(s):

Jan P. Christensen ◽

Peter C. Doherty ◽

Kristen C. Branum ◽

Janice M. Riberdy

Keyword(s):

T Cells ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

Memory T Cells ◽

Influenza Infection ◽

T Cell Memory ◽

Influenza A Viruses ◽

Cell Memory ◽

Cell Pool

ABSTRACT The recall of CD8+ T-cell memory established by infecting H-2b mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8+ effector and memory T cells specific for the shared, immunodominant DbNP366epitope were greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8+ memory T-cell pool (<0.5 to >10%) by sequential priming with two different influenza A viruses (H3N2→H1N1) gave much better protection. Though the H7N7 virus initially grew to equivalent titers in the lungs of naive and double-primed mice, the replicative phase was substantially controlled within 3 days. This tertiary H7N7 challenge caused little increase in the magnitude of the CD8+ DbNP366 + T-cell pool, and only a portion of the memory population in the lymphoid tissue could be shown to proliferate. The great majority of the CD8+ DbNP366 + set that localized to the infected respiratory tract had, however, cycled at least once, though recent cell division was shown not to be a prerequisite for T-cell extravasation. The selective induction of CD8+ T-cell memory can thus greatly limit the damage caused by a virulent influenza A virus, with the extent of protection being directly related to the number of available responders. Furthermore, a large pool of CD8+ memory T cells may be only partially utilized to deal with a potentially lethal influenza infection.

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Normal Numbers of Stem Cell Memory T Cells Despite Strongly Reduced Naive T Cells Support Intact Memory T Cell Compartment in Ataxia Telangiectasia

Frontiers in Immunology ◽

10.3389/fimmu.2021.686333 ◽

2021 ◽

Vol 12 ◽

Author(s):

Thomas J. Weitering ◽

Janine E. Melsen ◽

Monique M. van Ostaijen-ten Dam ◽

Corry M. R. Weemaes ◽

Marco W. Schilham ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Ataxia Telangiectasia ◽

Memory T Cells ◽

Spectral Flow ◽

Normal Numbers ◽

Cell Compartment ◽

Cell Memory ◽

Memory T Cell

Ataxia Telangiectasia (AT) is a rare inherited disorder characterized by progressive cerebellar ataxia, chromosomal instability, cancer susceptibility and immunodeficiency. AT is caused by mutations in the ATM gene, which is involved in multiple processes linked to DNA double strand break repair. Immunologically, ATM mutations lead to hampered V(D)J recombination and consequently reduced numbers of naive B and T cells. In addition, class switch recombination is disturbed resulting in antibody deficiency causing common, mostly sinopulmonary, bacterial infections. Yet, AT patients in general have no clinical T cell associated infections and numbers of memory T cells are usually normal. In this study we investigated the naive and memory T cell compartment in five patients with classical AT and compared them with five healthy controls using a 24-color antibody panel and spectral flow cytometry. Multidimensional analysis of CD4 and CD8 TCRαβ+ cells revealed that early naive T cell populations, i.e. CD4+CD31+ recent thymic emigrants and CD8+CCR7++CD45RA++ T cells, were strongly reduced in AT patients. However, we identified normal numbers of stem cell memory T cells expressing CD95, which are antigen-experienced T cells that can persist for decades because of their self-renewal capacity. We hypothesize that the presence of stem cell memory T cells explains why AT patients have an intact memory T cell compartment. In line with this novel finding, memory T cells of AT patients were normal in number and expressed chemokine receptors, activating and inhibitory receptors in comparable percentages as controls. Comparing memory T cell phenotypes by Boolean gating revealed similar diversity indices in AT compared to controls. We conclude that AT patients have a fully developed memory T cell compartment despite strongly reduced naive T cells. This could be explained by the presence of normal numbers of stem cell memory T cells in the naive T cell compartment, which support the maintenance of the memory T cells. The identification of stem cell memory T cells via our spectral flow cytometric approach is highly relevant for better understanding of T cell immunity in AT. Moreover, it provides possibilities for further research on this recently identified T cell population in other inborn errors of immunity.

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T cell memory is short-lived in the absence of antigen.

Journal of Experimental Medicine ◽

10.1084/jem.174.5.969 ◽

1991 ◽

Vol 174 (5) ◽

pp. 969-974 ◽

Cited By ~ 242

Author(s):

D Gray ◽

P Matzinger

Keyword(s):

T Cells ◽

T Cell ◽

Memory T Cells ◽

Immunological Memory ◽

Traditional View ◽

T Cell Memory ◽

Memory Cells ◽

Cell Memory ◽

Independent State ◽

Dependent Process

Immunological memory has generally been ascribed to the development of long-lived memory cells that can persist for years in the absence of renewed antigenic encounter. In the experiments reported here, we have adoptively transferred memory T cells in the presence and absence of priming antigen and assessed their functional survival. The results indicate that, in contrast to the traditional view, the maintenance of T cell memory requires the presence of antigen, suggesting that memory, like tolerance, is an antigen-dependent process rather than an antigen-independent state.

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