CD8+ cells and not CD4+ T cells are hyporesponsive to CD28- and CD40L-mediated activation in HIV-infected subjects

J Vingerhoets, L Kestens, G Penne, H De Vuyst, M Vandenbruaene, Y Pelgrom, E Bosmans, M de Boer, A Kasran, M Azuma, R Colebunders, JL Ceuppens, G Vanham

Research output: Contribution to journalA1: Web of Science-article

Abstract

T cell dysfunction in HIV-infected subjects could be the consequence of altered sensitivity of CD4+ or CD8+ T cells to various costimulatory signals. Therefore, we studied proliferation and cytokine production in highly purified CD8+ and CD4+ T cells from HIV-infected and HIV- subjects, induced by co-activation via cell-bound CD80, CD86 and CD40 or by allo-activation. Regardless of the nature of the first and the costimulatory signal, CD8+ T cells from patients proliferated consistently less than controls, while responses from CD4+ T cells were similar in patients and controls. This phenomenon was observed after ligation of CD28 combined with anti-CD3 or phorbol myristate acetate (PMA), but also after allogeneic stimulation and after activation by CD40 and anti-CD3. Anti-CD3 combined with CD80 or CD86 induced a mixed Th1/Th2-type cytokine profile in both CD4+ and CD8+ T cells from controls, whereas anti-CD3 plus CD40 induced only low levels of Th2-type cytokines and no interferon-gamma (IFN-gamma) in CD4+ T cells. Compared with controls, CD4+ T cells from patients produced slightly lower levels of IL-10 but equal amounts of IFN-gamma, IL-4 and IL-5, while CD8+ T cells from patients produced less of all cytokines tested. In conclusion, responses of purified CD4+ T cells from HIV+ subjects to various costimulatory pathways are relatively intact, whereas CD8+ T cells are hyporesponsive at the level of proliferation and cytokine production. A generalized intrinsic CD8+ T cell failure might contribute to viral and neoplastic complications of HIV infection
Original languageEnglish
JournalClinical and Experimental Immunology
Volume107
Pages (from-to)440-447
ISSN0009-9104
Publication statusPublished - 1997

Keywords

  • B780-tropical-medicine
  • Immunology
  • Antigens
  • CD28
  • CD4
  • Lymphocytes
  • CD8
  • HIV
  • Virology
  • Glycoproteins
  • Cytokines
  • T-lymphocytes
  • Th1 cells
  • Th2 cells

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