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Insulin-like growth factor I (IGF-I) has been implicated to play a regulatory role in T cell development and in T cell function. We investigated the expression of type I IGF receptors on human peripheral T cells related to the maturation and activation stage using the type I IGF receptor-specific monoclonal antibody alpha IR3. It appeared that 87% of the CD4+CD45RA+ cells and 66% of the CD8+CD45RA+ cells were alpha IR3+, whereas only 37% of the CD4+CD45R0+ cells and 38% of the CD8+CD45R0+ cells bound alpha IR3. We also found that the fraction of alpha IR3+ cells within in vivo or in vitro activated (HLA-DR+) T cells is markedly lower than in nonactivated (HLA-DR-) cells. In vitro phytohemagglutinin-activated T cells and CD4+CD45R0+ cells activated with recall antigens also contained less alpha IR3+ cells (1-6%) than nonactivated cells (30-54%).

A possible role of intercellular adhesion molecule 1 (ICAM-1, CD54) in transmembrane signaling was investigated in B cells from the Burkitt lymphoma cell line MTLM4. Cross-linking of membrane IgM (mIgM) induced an increase in intracellular free Ca2+ as a result of the release from intracellular stores and an influx of extracellular Ca2+. When the B cells were incubated with limiting concentrations of anti-IgM, co-ligation of mIgM and CD54, but not CD19, resulted in an inhibition of the Ca2+ response. Separate cross-linking of mIgM and CD54 under these conditions, using isotype mismatched monoclonal antibodies (mAb), did not affect the mobilization of Ca2+. The CD54-mediated inhibition of the Ca2+ response was also observed in the absence of extracellular Ca2+. All CD54 mAb tested (F10.2, F10.3 and F7.11) interfered with mIgM signaling. The results presented in this report imply that CD54 is linked to intracellular signaling pathways and, via co-ligation with mIgM, interferes in the release of Ca2+ from intracellular stores.

In this report we show that the major histocompatibility complex (MHC) class II-negative thymus of a bare lymphocyte syndrome (BLS) patient contains a reduced CD4+ CD8- T cell population when compared to thymocytes derived from a MHC class II-expressing thymus. Of these CD4+ CD8- BLS thymocytes, approximately only one third co-expressed the CD3 antigen, moreover at a lower expression level when compared to control thymocytes. This suggests a partial maturation of the CD4+ CD8- T cells in the absence of MHC class II expression. Among the BLS thymocytes, CD4+ CD8+ thymocytes could easily be detected. Noteworthy, the number of CD4- CD8+ thymocytes was significantly increased. CD4+ CD8- T cells could also be found among the BLS peripheral blood mononuclear cells, albeit at reduced numbers. Despite the absence of peripheral MHC class II expression, the majority of these CD4+ CD8- T cells co-expressed the CD45RO marker. In the BLS patient, thymocytes as well as peripheral CD4+ CD8- T cells were not restricted in the use of the available T cell receptor (TcR) V gene family pool. However, the lack of detectable levels of thymic and peripheral MHC class II antigen expression in the BLS patient had altered the CD4-skewing patterns of TcR V gene families which were present in normal individuals. In conclusion, the lack of MHC class II expression in the BLS patient does not completely inhibit the CD4+ CD8- T cell development.

Deoxyguanosine (dGuo) has been implicated as the toxic metabolite causing a severe impairment of cellular immunity in children with a genetic deficiency of purine nucleoside phosphorylase (PNP). In peripheral blood T cells of normal donors both the pathway which leads to phosphorylation of dGuo (ultimately resulting in deoxyguanosine triphosphate, dGTP) and the salvage pathway which starts with degradation of dGuo by PNP (resulting in the formation of guanosine triphosphate, GTP) contribute to the inhibition of proliferation. In normal peripheral blood B cells, addition of dGuo leads to an inhibition of proliferation and differentiation. The concentrations of dGuo needed to cause a 50% inhibition are equivalent for peripheral blood T cells and B cells. Inhibition of B cell differentiation can be observed at the level of intracytoplasmic as well as secreted Ig and concerns all Ig isotypes. The early phase of B cell activation which takes place during a 24-h preculture with formalinized Cowan I Staphylococci is not affected by dGuo; it is not until proliferation and differentiation of B cells, brought about by culturing in the presence of crude concanavalin A supernatant, occurs that inhibitory effects of dGuo become evident. Addition of dGuo to B cell cultures results in an intracellular accumulation of GTP and dGTP. Addition of 8-aminoguanosine, a PNP inhibitor, next to dGuo, completely prevents the dGuo-mediated inhibition. Under these circumstances the dGuo-mediated increase in intracellular GTP is abrogated while dGTP accumulation still occurs. This indicates that the inhibitory effect of dGuo on the proliferation and differentiation of peripheral blood B lymphocytes of normal donors is independent of dGTP accumulation.