T CELL HIPORESPONSIVENESS TO Mycobacterium tuberculosis INDUCED BY CD31: A ROLE FOR SAP?

QUIROGA MF; 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, ALAI 2005; 2005

ALAI

T cell hiporesponsiveness to Mycobacterium tuberculosis induced by CD31: a role for SAP? Quiroga MF, Pasquinelli V, Martinez GJ, Musella R, Castro Zorrilla L, Bracco MM, Malbrán A, Abbate E, Chuluyan HE, and Garcia VE. Department of Microbiology and Immunogenetics Division, UBA School of Medicine; Instituto Vaccarezza, UBA and Hospital Muñiz. National Academy of Medicine and Hospital Británico. 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.