Cross‐Talk between CD31 and the Signaling Lymphocytic Activation Molecule–Associated Protein during Interferon‐γ Production against Mycobacterium tuberculosis

Abstract

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.