Naive, activated, and effector/memory lymphocyte subsets at diagnosis and during the therapeutic course of childhood tuberculosis

W. A. Hanekom*, J. Hughes, E. Malan, S. Potgieter, Ram Yogev, I. J. Check, G. D. Hussey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Because inadequate data of lymphocyte subsets in childhood tuberculosis (TB) hamper understanding of protective host responses, we determined expression of HLA-DR and CD25 (IL-2R) (activation markers), CD45RA (naive cell marker) and CD29 (β1-integrin, effector/memory cell marker) on peripheral blood lymphocytes from 91 prospectively enrolled S.African children with pulmonary TB (median age 39 mos., range 3-171) at 0, 6 and 12 wks. At baseline patients with culture-positive TB (n=32), as compared to culture-negative patients, had lower HLA-DR and CD25 expression (p<0.0001), higher expression of CD45RA (particularly in CD4 cells: p<0.0001) and lower CD29 expression in total lymphocytes (p<0.0001). Altered surface marker expression persisted in culture-positive patients during therapy. In the entire cohort significant increases in HLA-DR and CD25 occurred only after 12 wks. (median CD3+DR+: 6.9%, 7.2% and 7.8% at 0, 6 and 12 wks.). The % CD45RA+ CD4 cells remained unchanged over time, whereas % naive CD8 cells increased (p<0.001). Largest increases in % CD29+ cells occurred in CD8 cells (20.7% vs. 27.5% at 0 and 12 wks., p<0.001). Conclusions: 1. Severe TB (culture-positive disease) is characterized by decreased immune activation, larger populations of naive cells, and lower numbers of effector/memory lymphocytes. 2. We previously reported a strong association between severe TB and low CD8 T cells, and that CD8 T cells expanded preferentially during therapy. Here we demonstrated that effector/memory cell expansion was also greatest in the CD8 cell population. These findings may point toward a role for CD8 T cells in protection against childhood TB, particularly severe disease. This is a surprising finding in view of the putative central role of CD4 T cells in host responses to M. tuberculosis.

Original languageEnglish (US)
Number of pages1
JournalClinical Infectious Diseases
Volume25
Issue number2
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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