LOCALIZATION IN-SITU OF COSTIMULATORY MOLECULES AND CYTOKINES IN B-CELL NON-HODGKINS-LYMPHOMA

Costimulatory molecules are essential in cognate interactions between T and B lymphocytes. To study the prerequisites of functional interact ions between malignant B cells and intermingled T cells in B-cell non- Hodgkin's lymphomas (B-NHL), we examined the expression of CD40, CD80 and CD86 and their ligands CD40 ligand (CD40L, CD154), CD28 and CTLA4 (CD152) using immunohistochemistry and confocal laser scanning microsc opy. Almost all mucosa-associated lymphoid tissue (MALT) NHL were posi tive for CD40 and CD80 and in nine out of 14 cases were positive for C D86. The majority of follicle centre cell lymphomas (FCCL) expressed C D40, but were heterogeneous in their expression of CD80 and CD86. Most diffuse large cell lymphomas (DLCL) were CD80(+), but lacked expressi on of CD86. These patterns reflect the differences in phenotype of nor mal marginal-zone B cells (as counterparts of MALT NHL) and germinal c entre cells (as counterparts of FCCL and DLCL). Counter-receptors on T cells were detectable in 13 of 14 MALT NHL, 12 of 16 FCCL but only oc casionally in DLCL (three of 12 cases). A subgroup of FCCL was identif ied with T-cell expression of CD40L, CD28 and CTLA4 simultaneously wit h strong expression of CD40 and CD86 on the tumour B cells. These resu lts indicate that MALT NHL and a subset of FCCL are most optimally equ ipped for functional interactions with T cells. This may be supported by the demonstration of cytokine production mainly in T cells - in MAL T NHL [interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-IO] and FCCL (IL-2, IFN-gamma) and to a lesser extent in DLCL.