Cross‐Talk between CD31 and the Signaling Lymphocytic Activation Molecule–Associated Protein during Interferon‐γ Production against Mycobacterium tuberculosis
1Department of Microbiology, Parasitology, and Immunology, University of Buenos Aires School of Medicine, 2Laboratorio de Inmunogenética, Hospital de Clínicas José de San Martín, University of Buenos Aires, 3División Tisioneumonología, Hospital FJ Muñiz, 4Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, 5Departamento de Alergia e Inmunología, Hospital Británico, Buenos Aires, Argentina; 6Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; 7Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)‐γ production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3+CD31+ blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN‐γ was secreted only by CD31− T cells. In contrast, in patients with weak Th1 cytokine responses to M. tuberculosis, the level of CD3+CD31+ lymphocytes was increased and IFN‐γ production was low. Furthermore, the inverse relationship between CD31 expression and IFN‐γ production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN‐γ inducer in tuberculosis. Interestingly, CD31 bound to SLAM‐associated protein (SAP), an IFN‐γ inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN‐γ response to M. tuberculosis. Thus, CD31, when binding to SAP, interferes with Th1 responses, suggesting that CD31 has a key regulatory role in the signaling pathway(s) leading to the IFN‐γ response to M. tuberculosis.
Received 10 March 2007; accepted 22 May 2007; electronically published 26 September 2007.
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Potential conflicts of interest: none reported.
Financial support: Agencia Nacional de Promoción Científica y Tecnológica (grant PICT 5‐9638 to V.E.G and grant PICT 15069 E.C.); Antorchas Foundation (support to V.E.G.), University of Buenos Aires (grant UBACyT M030 to V.E.G and grant M09 to E.C.), Consejo Nacional de Investigaciones Científicas y Técnicas (grant PIP 5584 to V.E.G).
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M.F.Q. and J.O.J. contributed equally to this work.
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V.E.G and E.C. contributed equally to this work.