Hodgkin’s Disease: A War Between T-Lymphocytes and Transformed Macrophages?

To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross- linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI- MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T- cell deficiency in patients with Hodgkin's disease.

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L428 cells derived from Hodgkin's disease produce E rosette-inhibiting factor

Blood ◽

10.1182/blood.v76.4.791.791 ◽

1990 ◽

Vol 76 (4) ◽

pp. 791-796 ◽

Cited By ~ 1

Author(s):

I Katay ◽

U Wirnitzer ◽

H Burrichter ◽

C von Kalle ◽

E Schell-Frederick ◽

...

Keyword(s):

T Lymphocytes ◽

Cell Line ◽

T Lymphocyte ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Target Cells ◽

Normal Peripheral Blood ◽

Inhibiting Factor ◽

C 30

Abstract Diminished rosetting capacity of T cells is a well-known phenomenon in Hodgkin's disease, and inhibitors of E rosette formation have been reported to be present in the plasma of patients with Hodgkin's disease. The cell line L428, representing an in vitro counterpart of Hodgkin and Sternberg-Reed cells, could be shown to release a factor capable of suppressing the binding of sheep red blood cells (SRBC) to normal peripheral-blood T lymphocytes or to a T-cell line (L735). At maximally effective concentrations, RIF (rosette inhibiting factor) inhibited T lymphocyte rosetting by approximately 40% (mean from 184 healthy controls). The diminished E rosetting of T lymphocytes from Hodgkin's patients was not further suppressed by added RIF. This factor inhibited binding of SRBC to their target cells at 37 degrees C but not at 4 degrees C. The factor could be stored lyophilized at -20 degrees C and was stable at 56 degrees C (30 minutes). RIF was inactive below pH 6 and above pH 9 or after trypsin digestion. Purification by affinity, ion exchange, and molecular sieve chromatography showed activity peaks at 12.5 Kd, 25 Kd, 50 Kd, and 100 Kd.

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