T-cell regulation of murine IgA synthesis.

In studies reported here, the polyclonal activator lipopolysaccharide was used to stimulate the synthesis and secretion of IgM, IgA, and IgG in cultures of mouse lymphoid cells. The total immunoglobulin of each class which resulted was measured by specific double-antibody radioimmunoassays. The effect of Con A-activated T cells from various tissues on such immunoglobulin synthesis was then assessed. Variations in regulatory T-cell activity among the various lymphoid tissues for IgA but not for IgM or IgG was observed. In particular, Peyer's patches T cells were found to contain a high level of IgA T-cell helper activity compared to that of spleen or peripheral lymph node. The independent variation of T-cell regulatory activity for IgA as compared to that for IgM and IgG among the different tissues is most consistent with there being a separate subset of T cells specifically regulating IgA. The significance of these findings for the understanding of the secretory immune system is discussed.

IgA-containing circulating immune complexes in dermatitis herpetiformis, Henoch-Schönlein purpura, systemic lupus erythematosus and other diseases.

The sera of patients with dermatitis herpetiformis, Henoch-Schönlein purpura and systemic lupus erythematosus were examined for IgA-containing immune complexes using a newly described radioimmunoassay. The IgG Raji cell radioimmunoassay and the 125I-C1q binding assay were also used to detect IgG- and IgM- containing soluble immune complexes. IgA-containing immune complexes were found in the sera of twelve of forty-nine (24%) patients with dermatitis herpetiformis, four of six (67%) patients with Henoch-Schönlein purpura, and seven of ten (70%) patients with systemic lupus erythematosus. IgG- or IgM- containing immune complexes were also found in six of forty-seven patients with dermatitis herpetiformis, in one of six patients with Henoch-Schönlein purpura, and in nine of ten patients with systemic lupus erythematosus, by either the 125I-Clq binding assay or the IgG Raji cell assay. The finding of soluble IgA immune complexes in a high percentage of patients with systemic lupus erythematosus and Henoch-Schönlein purpura suggests that they may play an important role in the pathogenesis of these diseases. In contrast, their low prevalence in patients with dermatitis herpetiformis suggests that IgA-containing immune complexes may not play a major role in the pathogenesis of dermatitis herpetiformis.

Genetic basis of gluten-sentitive enteropathy.

Families of patients with gluten-sensitive enteropathy (GSE) were typed for HLA-A and -B antigens as well as for HLA-DW3 antigen(s) using appropriate typing alloantisera. In addition, patients and families were typed for GSE-associated B cell antigens using alloantisera obtained from mothers and wives of patients. The data obtained suggest that disease occurs within families when two conditions were fulfilled: (1) the family member is homozygous for the GSE-associated B cell antigens and (2) the family member also bears the HLA-DW3 antigen(s) or an antigen usually associated with DW3. In addition, with the family studies it was possible to show that the gene(s) controlling the DW3 antigen(s) and those controlling the GSE-associated B cell antigens are separate nonlinked genetic loci, a fact which leads to the conclusion that GSE has a genetic basis in at least two genes. It is speculated that the genes responsible for GSE code for surface proteins which are physically associated on lymphoid cell membranes and which form receptors important to the initiation of disease.