Expression of CD40/CD40 ligand and bcl-2 family proteins in labial salivary glands of patients with Sjogren's syndrome

Lymphocytes infiltrating the salivary glands of patients with Sjogren's syn drome (SS) are activated and resist apoptosis. We determined the role of in teractions between CD40 and CD40 ligand (CD40L) in these infiltrating lymph ocytes on B-cell differentiation and expression of Bcl-2 family proteins. T en human T-cell leukemia/lymphoma virus-1 (HTLV-1)-seronegative and eight H TLV-l-seropositive SS patients were examined in the present study. Immunohi stochemistry was performed to examine the expression of CD3, CD20, PCA-1, C D40, CD40L, Bcl-2, Bar, and Bcl-x on T and B lymphocytes infiltrating labia l salivary glands of SS patients. We also examined the expression of CD40 a nd CD40L on peripheral blood lymphocytes of the same patients by using flow cytometry. CD40L was not expressed on peripheral blood lymphocytes of SS p atients. Peripheral blood B cells but not T cells expressed CD40, In contra st, >50% of mononuclear cells, including T and B cells infiltrating the gla nds, expressed CD40. In addition, a clear expression of CD I OL in both inf iltrating T cells and B cells, and that of PCA-I, was also demonstrated. Su rprisingly, the expression of Bcl-2 and Bcl-x was colocalized with that of CD40 determined by mirror section technique. Bcl-x was also abundantly expr essed on infiltrating mononuclear cells, but, Pax expression was relatively less than that of Bcl-2 or Bcl-x. The expression of the above molecules wa s not different between HTLV-l-seronegative and HTLV-l-seropositive SS pati ents. Our results indicate that CD40/CD40L pathways could be augmented in s alivary glands of SS patients, inducing B-cell differentiation to PCA-1+ pl asma cells. Immunohistochemical analysis also suggests that signaling throu gh CD40 by means of CD40L increases the expression of Bcl-2 as well as Bcl- x in infiltrating lymphocytes, providing the resistance against apoptosis. Our findings were commonly observed in SS patients irrespective of HTLV-I s eropositivity.