Lymphocytes Bearing Either γδ-TCR or αβ-TCR Can Recognize Non-MHC Encoded CD1 Molecules

Abstract

Two T cell populations exist which express distinct T cell receptors (TCR), TCR a 13 (Marrack and Kappler, 1986) and TCR γδ (Brenner et al. 1986). T cells bearing the TCR αβ complex are numerically predominant in the blood and organized lymphoid organs and recognize foreign peptides presented in the context of self-major histocompatibility complex (MHC) molecules. As mature lymphocytes, they are “single positive” and express either CD4 or CD8 which participate in recognition of MHC class II or class I molecules, respectively. In contrast, the recognition specificity of lymphocytes bearing the γδ-TCR are unknown, and these cells are frequently both CD4 and CD8 negative (“double negative”) (Groh et al. 1988). Besides γδ-TCR lymphocytes, a population of CD^-4^- lymphocytes bearing the αβ-TCR also exists in man (Shivakumar et al. 1989). In cytofluorographic analyses, staining with anti-CD4 together with anti-CD8 in one color compared to staining with anti-CD3 in a second color, we observed the expected presence of a subpopulation of CD3⁺CD^-8^- cells in human peripheral blood. When also staining with mAb anti-TCRδ1 (pan TCR γδ reactive), a majority of these double negative T cells were shown to bear the γδ -TCR. However, in all normal subjects examined a population of 0.5–2.0% of these CD4^-8^- T cells was found to lack reactivity with anti-TCRδ1. These cells were isolated and were shown to express the αβ-TCR. CD4^-8^- TCR-αβ bearing cells have been reported to be increased in number in certain genetically autoimmune strains of mice that have generalized lymphadenopathy (gld, L pr) (Miescher et al. 1987). These mice share some clinical features in common with the human autoimmune disease systemic lupus erythematosus (SLE) where an increase in the number of CD4”8” T cells in peripheral blood has also been found (Shivakumar et al. 1989). Our analyses suggest that the number of double negative αβ-TCR bearing lymphocytes were increased and represented more than 10% of the CD3⁺ cells in several individuals with SLE. Thus the CD3⁺4^-8^- phenotype occurs on a majority of αβ-TCR lymphocytes and on a small fraction of αβ-TCR bearing lymphocytes, particularly in SLE.