Phenotypical and Functional Characterization of Double‐Negative (CD4‐CD8‐) αβ T‐Cell Receptor Positive Cells from an Immunodeficient Patient

We have characterized CD4-CD8- double-negative (DN) αβTCR+ T cells from a patient with immunodeficiency, lymphocytosis, lymphadenopathy, and hepatosplenomegaly. The majority of peripheral blood lymphocytes were DN αβTCR+ T cells as evalualed by FACS and biochemical analysis. The DNT cells showed the following phenotype: αβTCR+, γδTCR-, CD2+, CD3+, CD57+, and HLA-DR+. Both southern blot analysis of TCR genes and F ACS analysis applying a panel of Vβ and Vα monoclonal antibodies (MoAbs) indicated a polyclonal T-cell expansion. Thymic biopsy showed normal histology, whereas lymph node biopsy samples showed altered histological and immunohistoiogical patterns with markedly expanded paracortical areas containing the DN T ceils of the same phenotype as found in peripheral blood T cells. In functional studies, the DN T cells showed a profoundly reduced proliferative response upon stimulation with mitogens as well as MoAbs against the TCR /CD3 complex. CD2. and CD28, respectively, Addition of exogenous interleukiri-2 (IL-2) only minimally augmented the proliferative response. In contrast, the addition of a combination of Ca2+ ionophore and phorbol 12-myristate 13-acetaie (PMA) restored the proliferative response of the DM T cells to almost normal levels. This observation strongly suggests that the protein kinase C activity of the DN T cells was intact, but that the normal mechanism for transmembrane signal transduction was impaired in these unusual DN T cells.