Increased Cell Surface Expression of a Newly Identified Heterodimer on Activated Blastic T Cells

Abstract

A hybridoma (F6C7) was established by fusing NS1 cells with spleen cells of MRL/Mp-+/+(MRL/+) mice suffering from Ipr-GVHD. This F6C7 mAb (IgG2b, κ) stains a broad spectrum of blood cells at varying intensities in mice and rats. In normal (BALB/c) mice, granulocytes and B cells are highly positive for F6C7-reactive Ag (F6C7-Ag). Thymocytes and peripheral (CD4 + and CD8 +) T cells show negative to low intensities. These staining profiles are similar in C57BL/6, AKR/J, C3H/HeJ, and MRL/+ mice. When spleen cells were activated in vitro, a blastic cell population of autoactivated CD4 + and CD8+ T cells showed increased F6C7-Ag expression. Alloactivated CD4 + blastic T cells also showed increased expression of F6C7-Ag, whereas alloactivated CD8 + blastic T cells as well as Con A-activated CD4 + and CD8 + blastic T cells remained at the level of small (nonblastic) cells. These findings suggest that the surface expression of F6C7-Ag is up-regulated in some activation processes of T cells, particularly in autoactivation. Young (2-month-old) MRL/Mp- Ipr/Ipr (MRL/ Ipr) mice show staining profiles of F6C7-Ag similar to those of normal mice, except that many more blastic (CD4 + and CD8 +) T cells show high F6C7-Ag expression than those of normal mice. A small but significant number of CD4 +F6C7-Ag high and a much higher number of CD8 +F6C7-Ag high blastic T cells were observed in the spleen cells of MRL/+ mice suffering from Ipr -GVHD. These blastic T cells may exert autoreactivity and participate in the initiation of autoimmune diseases, lymphadenopathy, and Ipr-GVHD. Immunoprecipitation and SDS-PAGE revealed that F6C7-Ag is a heterodimer comprised of approximately 78- and 70-kDa molecules without disulfide bonds.