Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

Abstract

A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of a-and 8-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen I (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity. In addition, lymphocyte function deficiencies previously unobserved in this disease were found. Cytolytic T lymphocyte activity was profoundly reduced; a-and y-interferon production were impaired. Finally, there was no antibody production to vaccinal antigens whereas the antibody responses to polysaccharides and to cytomegalovirus were found to be normal. The cytotoxic T cell deficiency could be expected from previous blocking experiments of this function with monoclonal antibodies to LFA-1 and is probably related to an extremely severe deficiency in LFA-1 expression in this patient. Anomalies in interferon and in antibody production suggest additional role(s) of the LFA-1 complex in monocyte/T lymphocyte/B lymphocyte cell interactions that have not yet been envisaged.

LFA‐1 β‐chain synthesis and degradation in patients with leukocyte‐adhesive proteins deficiency

“…Deficiency in the expression of LFA-1, Mol and p150,95 on bone marrow-derived cells leads to defective mobilization of polymorphonuclear cells and monocytes into inflammatory sites and subsequently to recurrent bacterial lifethreatening infections (16-141, reviewed in [12,131). In the majority of cases, this severe disorder is of autosomal recessive inheritance [9, 11,131. Previous studies on the molecular defect underlying the disease have mainly implied the use of monoclonal anti-a and anti$ chain antibodies (mAb TS 1 Springer et al [9, 121.…”

Down‐regulation of LFA‐1‐mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol‐3‐kinase activity

“…The anti-LFA-1 Ab (25.3, IgG1) was purchased from Immunotech (Marseille, France) [25]. The anti-p85 P13-kinase Ab was a polyclonal Ab purchased from Upstate Biotechnology Inc. (Lake Placid, NY).…”

Possible T4‐HLA class II interaction as an essential event in antigen‐specific helper T lymphocytedependent B cell activation

“…They were obtained from G. Goldstein. A mAb 39C8 reacting with CD2 was used as supernatant [20]. Several mAb specific for monomorphic epitopes of HLA class I1 molecules were used: 1-35 (IgG2,) [21], CA206 (IgG2,), CA 141 (IgG2,), [22].…”

“…Several mAb specific for monomorphic epitopes of HLA class I1 molecules were used: 1-35 (IgG2,) [21], CA206 (IgG2,), CA 141 (IgG2,), [22]. A purified mAb specific for the subunit of LFA-1 (25-3) (IgG1) [20] was a gift of D. Olive. Finally, a mAb specific for the B cell-specific CD20 antigen was RFB7 (IgM), a kind gift from G. Janossy.…”