Monoclonal Antibodies in the Characterization of Human T and Large Granular Lymphocytes* Fernando Aiuti, M.D. Franco Pandolfi, M.D. Department of Clinical bnmunology, Universitd delia Sapienza, Rome 00161, Italy In recent years, the development of monoclonal antibodies against human lymphocytes has brought considerable insight into the complex network of different subpopulations which interact and are required for a proper im- munological response. The quantity of data thus obtained has elucidated the relationship pattern between discrete subpopulations present in normal donors and alterations observed in many pathological conditions. A careful interpretation of these results is required. For instance, the most frequent erroneous assumption is that of considering the expansion of a given antigen as strictly related to the capacity of the positive cell of per- forming a given function. Several antigens that are identified by monoclonal reagents have been de- scribed on human T cells, and T-cell subpopulations are capable of mediat- ing different regulatory functions such as helper, suppression, or B-cell dif- ferentiation. Helper T cells are in- cluded in subpopulations identified by some monoclonal reagents (i.e., Leu 3a or OKT4), but this does not neces- sarily mean that all the normal Leu 3a + or OKT4 + cells are helper cells. In addition, the issue is complicated by the fact that in pathological condi- tions (such as lymphoproliferative dis- orders or in primary immunodeficien- cies) the expression of these antigens or the ability to perform a given function may be altered by the dis- ease. With such limitations, however, monoclonal antibodies are helpful re- agents for basic and clinical im- munologists. In this review we will * Supported by a grant from the "Ministero della Pubblica Istruzione, Ricerca Scientifica" 1981. focus on human T cells and large granular lymphocytes (LGL) as iden- tified by monoclonal reagents in nor- mal donors and in some pathological conditions. Identification of T Cells and Large Granular Lymphocytes in Normal Donors Current terminology refers to the cells of thymic origin situated in the secondary lymphoid organs as peripheral T lymphocytes, and thymic cells are usually referred to as thymo- cytes. Large granular lymphocytes are medium to large size lymphocytes with azurophilic granules in their cy- toplasm which mediate natural killer activity. Thus far, no conclusive evi- dence has been obtained demonstrat- ing that LGL belong to any of the known hemic lineages. Since these cells share some surface markers with T lymphocytes and monocytes, it has been postulated that they may belong to the T lineage, the myelomonocytic lineage, or to a separate cell lineage. T Lymphocytes Three main groups of monoclonal reagents directed against antigens ex- pressed by T cells have been devel- oped (Table I). The first group in- cludes antigens expressed by all the thymocytes and peripheral T cells. Some reagents in this group (9.6 and OKTI 1) (2) are directed against the membrane receptor for sheep erythro- cytes which mediates the function of E-rosettes by T ceils. Others (10.2 and Leu 1) identify a separate antigen. The second group consists of monoclonal antibodies that identify antigens expressed on many thymo- cytes and on a subpopulation of peripheral T cells. These reagents are of particular importance because among these subpopulations are re- stricted ceils with immunoregulatory functions. Thus, helper T cells are comprised among OKT4, 9.3, and Leu 3a cells, whereas suppressor T cells are restricted to OKT5, OKT8, and Leu 2a cells. Another commonly used is reagent 3A1. Among 3A1 cells are comprised helper and induc- ible suppressor T cells. A different issue is represented by antigens expressed by T cells at early differentiation stages. For instance, OKT6 recognizes an antigen present on thymocytes but not on mature peripheral T lymphocytes. Table 1 Antigens Recognized by Monoclonal Antibodies Expressed by Human T Cells %'Peripheral Designation Molecular Weight % Thymocytes T Cells Notes First group (all thymocytes and peripheral T cells) 9.6 50,000 100 100 OKT I 1 I0.2 67,000 100 100 Leu 1 66,000 100 I00 Second group (minority of thymoeytes and all peripheral T cells) Leu 4 20-30,000 80 95 OKTI 65,000 10 100 OKT3 19,000 20 95 UCTH 1 -- 40 95 Third group (many thymocytes and a subpopulation of T cells) OKT4 62,000 90 65 9.3 44,000 40 65 Leu 3a 55,000 80 50 OKT5 32,000 90 20 OKT8 33,000 90 30 Leu 2a 32-42,000 80 25 3AI 40,000 100 85 Sheep receptor Helper T cells Suppressor T cells Helper and inducible T cells 32 Clinical Immunology Newsletter