Human Ia Alloantigens as Cell‐Differentiation Markers of Normal and Pathologic Leukocyte Surfaces

Abstract

Comparative membrane phenotypes of normal T and B lymphocytes, of normal myeloid cells, and of various leukemic cell types were established by the use of specific Ia‐type alloantisera and ‘classical’ immunological surface markers, including complement receptors. 4%–8% of lymphocytes taken from mixed leukocyte cultures on day 4 showed Ia alloantigens of responder‐type specificity, in addition to two known T‐cell markers on the same cell surface. Together with Ia antiserum inhibition studies, this subpopulation would appear to present a human mixed leukocyte culture (MLC)‐related suppressor T‐cell population. Whilst such cells could not be detected in normal peripheral blood by double fluorescence, a small percentage could readily be demonstrated among cell populations from patients with systemic lupus erythematosus and rheumatoid arthritis (joint fluid). Specific Ia alloantigens were further detected on the immature myeloid cells from bone marrow but not on the more mature myeloid cell types. This establishes the Ia alloantigen system as a valuable cell surface differentiation marker in man. The appearance of complement receptors on myeloid cells was Later than that of Ia alloantigens. Ia alloantigens are expressed on various numbers of leukemic myelo‐ and lympho‐blasts of the so‐called ‘non‐T, non‐B’ cell types. After discontinuous Ficoll gradients to enrich specific density cell groups, mainly the Ia alloantigens and the complement receptors allow a discrimination between acute (AML) and chronic myelocytic leukemia (CML) blasts, inclucling blasts crisis cells. AML cells appear to present a less differentiated cell type than CML blasts crisis cells. For the Latter disease, a more complex picture is obtained since at least three different membrane phenotypes of blasts cells can be identified: an Ia‐positive and an Ia‐negative myeloid blasts and an Ia‐positive lymphoid blasts. The relative quantities of these three elements can vary considerably within even a small group of patients.

Lack of correlation between lymphocyte activating determinants and HLA-DR on acute leukaemias

“…The absence of DR from myelocytes (Janossy et al, 1977;Wernet et al, 1977;Ross et al, 1978) implies that LAD may be expressed independently of DR. It is also possible, however, that a minor DR + population co-purifying with myelocytes is highly stimulatory, as for instance are dendritic cells (van Voorhis et al, 1982), or that blasts expressing DR are intrinsically suppressive.…”

The Comparison between Normal and Epstein‐Barr Virus‐Transformed Homozygous Typing Cells and Their Use for MLC, PLT and Serological Detection of Human Ia‐Type Alloantigens

“…In man, Mese antigenic determinants are found on the surface of all B lymphotcyte subclasses, but, except for suppressor T cells, they cannot be detected on T lymphocytes , 1977. More detailed information about the HLA-D antigens can be obtained by primed lymphocyte typing (PLT) which takes advantage of the specific memory of the cells primed in the MLC (Sheehy et al 1975, Sheehy & Bach, 1976,Wernet 1977. For such PLT experiments homozygous typing cells (HTC) turned out to be very useful because only the HLA-D homozygous cells allow a clearcut definition of the HLA-D determinants used as the priming agent.…”