Variant CD45R expression with autosomal dominant inheritance affects both helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) T cell populations.

The differential expression of various membrane CD45R isoforms by normal lymphocyte populations is known to be closely associated with distinct immunoregulatory functions. Abnormal patterns of CD45R expression have been reported in patients with common variable immunodeficiency and HIV infection, and recent evidence has suggested the possibility that one type of variant CD45R expression may be inheritable. By multiple colour flow cytometry, we studied the immunological characteristics of CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in a family with variant CD45R expression over three generations. This variant pattern of CD45R expression was shown to affect both CD4+ and CD8+ lymphocyte populations in individual family members and was immunologically characterized by a failure of the normal reciprocal expression of the CD45RA and CD45RO isoforms. Family studies also revealed that this trait had an autosomal dominant mode of inheritance and, in the heterozygous state, appeared not to be associated with major clinical abnormalities. The different isoforms of CD45 show distinct patterns of expression during lymphocyte ontogeny and activation, and these patterns appear to closely reflect function. Despite their diverse immunological roles, our finding that both CD4+ and CD8+ T cells in affected family members showed the same defect suggests a common regulatory mechanism(s) for both these lymphocyte populations. The recognition of this abnormality, particularly in homozygous individuals, will be of great importance in understanding the role of these molecules in immune function and disease.