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Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia

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Abstract

Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative responses to mitogens. We examined the distribution of T lymphocytes expressing distinctive surface Ag characteristic of “naive” (CD45RA+) and “memory” (CD29+, CD45RO+) T cells, in both CD4+ and CD8+ (bright and dim) lymphocytes from 13 AT patients, compared with healthy agematched controls. We found that, irrespective of age, patients with AT had a severe deficiency of CD4+/CD45RA+ lymphocytes. This decrease accounted for the reduction of total CD4+ cells, since the absolute numbers ofmemory CD4+ cells were not significantly different in AT and in controls. Functional tests revealed poor proliferative responses to phytohemagglutinin and normal responses to soluble Ag (tetanus toxoid) in AT patients. These data fit with the distribution ofnaive andmemory cells, which are known to respond predominantly to mitogens or to recall Ag, respectively. CD45RA molecules were normally expressed on CD8+ lymphocytes. This rules out a generalized defect of regulation or differential splicing as the cause of defective expression of CD45RA on CD4+ cells. The selective deficiency of CD4+CD45RA+ may provide a cellular basis for some functional T-cell abnormalities of AT patients. Furthermore, it might practically serve for an early, or even prenatal, diagnosis of this disease.

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Authors and Affiliations

  1. Department of Allergy and Clinical Immunology, University “La Sapienza”, Roma, Italy

    Roberto Paganelli, Enrico Scala, Elisa Scarselli, Daniela Carmini, Fernando Aiuti & Massimo Fiorilli

  2. Laboratorio Analisi, Ospedali Civili Riuniti, Venice, Italy

    Claudio Ortolani

  3. Department of Immunology, University of Modena, Modena, Italy

    Andrea Cossarizza

Authors
  1. Roberto Paganelli
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  2. Enrico Scala
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  3. Elisa Scarselli
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  4. Claudio Ortolani
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  5. Andrea Cossarizza
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  6. Daniela Carmini
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  7. Fernando Aiuti
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  8. Massimo Fiorilli
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Paganelli, R., Scala, E., Scarselli, E. et al. Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia. J Clin Immunol 12, 84–91 (1992). https://doi.org/10.1007/BF00918137

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  • DOI: https://doi.org/10.1007/BF00918137

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