T cell hyporesponsiveness to Mycobacterium tuberculosis induced by CD31: a role for SAP?

QUIROGA MF; JURADO JO; PASQUINELLI V; MARTINEZ GJ; MUSELLA R; CASTRO ZORRILLA L; BRACCO MM; MALBRÁN A; ABBATE E; CHULUYAN HE; GARCIA VE

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

SAI

CD31, a glycoprotein expressed by certain T cells, contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) similar to the tyrosine-based switch motif (ITSM) present in SLAM (signaling lymphocytic activation molecule). Since the SLAM-associated protein (SAP) binds to SLAM through its ITSM, it was suggested that SAP might interact with CD31, modulating its signaling. We investigated CD31-SAP interaction, and the effect of CD31 ligation on M. tuberculosis (Mtb)-stimulated T-cells in tuberculosis (TB) patients and healthy donors (HD). Engagement of CD31 by PECAM 1.2 monoclonal antibody inhibited in vitro IFN-g production (as measured by ELISA) from Mtb-stimulated peripheral blood mononuclear cells from TB patients and HD (p<0.05). CD31 also inhibited IFN-g production after OKT3 stimulation in both groups of individuals (% inhibition:30,5%±13,3; 52,3%±18,1; p<0.05). Furthermore, by immunoprecipitation analysis, we found a steady association between CD31 and SAP in T cells from TB patients and HD in response to Mtb. Interestingly, the inhibitory effect of CD31 was not observed in XLP patients (X-linked lymphoproliferative syndrome), individuals with non-functional SAP (% inhibition:5,4 ± 19,8, p<0.05). Our results show for the first time that CD31 might inhibit specific T cell responses in a SAP-dependent manner.