Expansion of clonotype-restricted HLA-identical maternal CD4+ T cells in a patient with severe combined immunodeficiency and a homozygous mutation in the Artemis gene.

We have observed a male infant with severe combined immunodeficiency (SCID) responsible for Artemis gene mutation, in whom marked expansion of the transplacentally grafted maternal CD4(+) T cells was observed in various tissues. His class I and II major histocompatibility antigens (MHC) were identical to his mother's. We analyzed the T-cell populations within target tissues at a molecular level in order to determine whether different T-cell clonotypes are expanded in different types of tissue. Prior to T-cell expansion, the T-cell receptor variable beta (TCRBV) 5.1 subfamily predominated in peripheral blood (PB) lymphocytes. Third complementarity determining region (CDR3) size spectratyping and amino acid sequencing showed that the range of T-cell clonotypes was very restricted. After T-cell expansion, different TCRBV subfamilies were found to predominate in different target tissues; these included TCRBV 5.1 and 17 in the PB, TCRBV 13 and 21.3 in the bone marrow, and TCRBV 17 in lymph nodes. CDR3 size analysis showed that the expression of different proliferating T-cell clonotypes remained restricted after T-cell expansion. These results indicate that highly restricted maternal T-cell clonotypes can markedly expand, possibly in response to tissue-specific antigens, in a MHC-identical recipient.