Signal transduction in human tumor infiltrating lymphocytes

In the present study we demonstrate that the CD28 activation pathway was functional in human tumor infiltrating lymphocytes (TIL), as it could induce a strong proliferation. On the other hand, a mitogenic combination of anti-CD2 monoclonal antibodies (MoAb) induced a slight proliferation of TIL isolated from lung but not from renal cell carcinoma (RCC). It is to note that CD28 triggering led to calcium mobilization, whereas stimulation via CD2 did not. Moreover, in most cases no synergistic effect between CD2 and CD28 activation pathways could be observed. Phenotypic analysis showed that freshly isolated TIL were mostly CD3+, LAM1+ and CD45RO+. Upon stimulation with anti-CD28 MoAb, the majority of cells lost LAM1 antigen and coexpressed both high (CD45RA) and low (CD45RO) molecular weight isoforms of CD45 molecule. By contrast, among CD2-activated TIL, a small fraction was LAM1+ and less than 10% coexpressed CD45RA and CD45RO antigens. Noteworthy, the CD45 molecule could regulate the CD28-induced calcium mobilization, as demonstrated by cross-linking of CD45RO, but not CD45RA, isoforms before challenging TIL with anti-CD28 MoAb.