Addiction of anti-CD28 antibodies restores PBMC proliferation and IFN-gamma production in lepromatous leprosy patients.

Abstract

During antigen recognition, T lymphocytes are primed by a physical interaction with antigen-presenting cells (APC). At least two signals are needed to activate T cells. One is provided by T cell receptor (TCR)/CD3 in the context of the mayor histocompatibility complex (MHC), and another signal is mediated by antigen-independent molecules, that is T cell membrane-bound CD28 and its specific ligand B7-1 (CD80) present in APC. Both signals trigger a series of metabolic events initiating right at the cell membrane and ending with activation and proliferation of T cells as well as specific cytokines synthesis. Our main goal was to determine whether deficiency in interferon-gamma (IFN-gamma) production shown by peripheral blood mononuclear cells (PBMC) from lepromatous leprosy (LL) patients, could be overcome by reconstituting in vitro the appropriate signals (by means of addition of anti-CD28 and anti-CD80 monoclonal antibodies). We also determined the stimulation index (SI) in the same PBMC. Our results demonstrated no significant differences in CD80 expression monocytes and B lymphocytes from LL patients when compared with healthy subjects. Nonetheless, CD28 expression significantly decreased in lymphocytes from LL patients (p < 0.01). Regarding IFN-gamma levels and SI, LL-PBMC failure before mitogenic stimuli could be reversed by further incubation with anti-CD28 antibody, but stimulation by specific antigen of Mycobacterium leprae was not changed. Addition of anti-CD80 antibody significantly increased IFN-gamma levels in phytohemagglutinin (PHA)-stimulated PBMC, although proliferation deficiency persisted. Cells stimulated with specific antigen did not modify either their proliferation or IFN-gamma levels.

• Authors: M Fafutis-Morris, C M Guillén-Vargas, S Navarro-Fierros, F Alfaro-Bustamante, G Zaitzeva-Petrovna, A Daneri-Navarro, L Santoscoy-Tovar, J Armendariz-Borunda
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 19 Issue 11 Pg. 1237-43 (Nov 1999) ISSN: 1079-9907 [Print] United States
• PMID: 10574615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• B7-1 Antigen
• CD28 Antigens
• Phytohemagglutinins
• Interferon-gamma

Topics

• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• B-Lymphocytes (immunology)
• B7-1 Antigen (immunology)
• CD28 Antigens (immunology)
• Cell Division (immunology)
• Female
• Humans
• Interferon-gamma (biosynthesis)
• Leprosy, Lepromatous (metabolism, pathology, therapy)
• Leukocytes, Mononuclear (immunology, pathology)
• Male
• Middle Aged
• Phytohemagglutinins (pharmacology)
• T-Lymphocytes (immunology)