Defective CD2 pathway T cell activation in systemic lupus erythematosus

Abstract

CD2 ('Ill; sheep erythrocyte receptor) is the surface component of an alternative, antigen-independent pathway of human T cell activation. The response to certain anti-CD2 antibodies is relatively independent of accessory cell signals and therefore provides a direct measurement of T cell function. The CD2 pathway may be important in the differentiation of thymocytes, on which the expression of CD2 precedes the appearance of the CD3-T cell receptor complex. In view of the impaired T cell regulation of immune responses in patients with systemic lupus erythematosus (SLE), we examined the activation of peripheral blood lymphocytes by anti-CD2 antibodies in 57 SIX patients and 32 normal control subjects. The CD2 pathway response was lower in the SLE patients (P < 0.0001); 18 of the 57 SLE patients had a lower response than any of the control subjects. The SI,E low-responder patients did not differ from the normal-responder patients in terms of disease activity or use of antiinflammatory and immunosuppressive medications. Low responses to anti-CD2 were corrected to normal by the coaddition of a submitogenic amount of phorbol myristate acetate (1 ng/ml). In some

Immune cell signaling aberrations in human lupus

“…Similarly, the decreased responses of lupus T cells to anti-CD2 (58) are reversed in the presence of adequate CD28-mediated stimuli provided either by B cells from normal donors or by an anti-CD28 MAb (59). In lesional skin of patients with SLE and discoid lupus, but not in normal skin, an abundance of CD80 and CD86 expressing cells in the dermis and epidermis has been observed (60,61), whereas the majority of infiltrating T cells are CD28 + (61).…”

A Splice Variant of the TCR ζ mRNA Lacking Exon 7 Leads to the Down-Regulation of TCR ζ, the TCR/CD3 Complex, and IL-2 Production in Systemic Lupus Erythematosus T Cells

“…T cells are considered to be central to the pathogenesis of SLE because a dysfunction in their regulatory action may be responsible for the altered immune responses and overproduction of pathogenic autoantibodies (6). Abnormalities in peripheral blood T cells (PBTs) from SLE patients include T lymphocytopenia, low proliferative responses to lectin, anti-CD3 and anti-CD2 stimulation (7,8), and a lower production of Th-1 type cytokines, such as IL-2 (9 -11). Although the costimulatory pathway is up-regulated, the TCR/CD3 pathway appears to be downregulated (12,13).…”

The T cell enigma in lupus

“…Some experiments have also been performed in the presence of costimulators, such as PMA, IL-1, IL-2, or a Ca++ ionophore. With notable exceptions (58-60), the weight of recent evidence seems to indicate that receptor-initiated signaling in lupus T cells is defective (61)(62)(63)(64), based on various measures of activation. However, addition of mitogenic or submitogenic concentrations of PMA to anti-CD3 normalizes indicators of T cell activation (65,66), such as IL-2 production.…”