Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens.

Abstract

It has been shown in the mouse that antigen triggers distinct subpopulations of thymusderived lymphocytes to express specific immunoregulatory activities, and that these activities are mediated in part by intercellular signals involving products of the I-region (Ia antigens) of the major histocompatibility complex. Thus, discrete Ia antigens have been detected on soluble T-cell factors which have either helper (1) or suppressor (2) activities, and are also present on the surface membrane of suppressor T cells (3), and Con A-induced T-cell blasts (4).Although Ia antigens have been generally thought not to be expressed by normal or leukemic T cells in man (5, 6), this view was re-examined when we found that antibody to a human Ialike antigen, p23,30 occasionally reacted with leukemic blasts which also expressed thymusdependent markers, p23,30 is a glycoprotein complex of 23,000 and 30,000 dalton subunits, isolated from the papain-solubilized membrane of a human lymphoblastoid B-cell line (7). A rabbit anti-p23,30 serum binds to peripheral B cells, monocytes, and a subpopulation of null cells, but is unreactive with normal human T cells or thymocytes (6,8). In addition to conforming in molecular weight and normal tissue distribution with murine Ia antigen, the detergent-solubilized form of p23,30, p29,34, reacts with B-cell alloantisera which are specific for determinants coded by the HLA-D locus, or I-region counterpart in man (9).We report here that determinants recognized by anti-p23,30 are expressed on the surface membrane of T cells which are transformed by alloantigen in mixed leukocyte culture (MLC), but are not detectable on T cells which are either freshly purified or maintained without stimulation in culture for 6 days. Moreover, allosensitized T cells were shown to elaborate and to incorporate into their surface membranes a 29,000 and 34,000 dalton, HLA-D-related complex, Materials and MethodsIsolation of Human TLymphocytes. T cells were isolated from peripheral blood mononuclear cells by nylon wool purification followed by formation and density gradient sedimentation of sheep erythrocyte-rosetting cells (10).Sensitization Cultures. T cells were sensitized to aUogeneic mitomycin-C-treated mononuclear cells (10). Of the cells recovered after a 6-day sensitization, greater than 98% were reactive with a heterologous antiserum which was specific for thymus-derived lymphocytes.

Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression.

“…In man, Ia determinants are expressed on the surface of B cells, monocytes, and a subset of Null cells (1)(2)(3)(4). In contrast, Ia antigens are not readily detectable on T cells or are, at best, expressed on an extremely small percentage of resting T lymphocytes (4)(5)(6). Perhaps of greater importance is the recent finding by several laboratories that activated human T cells express Ia antigens (5,6).…”

“…Perhaps of greater importance is the recent finding by several laboratories that activated human T cells express Ia antigens (5,6). Several observations point to the fact that these Ia antigens are intrinsic to the T cells and are not passively absorbed: (a) the demonstration of Ia + T-cell leukemias; (b) the finding that Ia antigens expressed by alloactivated T cells in mixed lymphocyte culture (MLC) 1 are of the responder and not the stimulator DR specificity; and (c) activated T cells biochemically synthesize Ia antigens de novo (4)(5)(6)(7)(8).…”

IL-2-mediated T cell proliferation in humans is blocked by a monoclonal antibody directed against monomorphic determinants of HLA-DR antigens.

“…For example, HLA-DR (or Ia) antigens have been demonstrated on the surface of >60% of MLC T cells, whereas <6% of normal T cells have been found to be positive for these markers (3)(4)(5). Similarly, 4F2 antigen, a 120,000-mol wt protein normally found in peripheral blood monocytes (6), is not detectable in resting T cells, but is expressed in MLC stimulated T cells (7,8).…”

MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells

“…n the late 1970s, the laboratories of Schlossman and Kunkel (1,2) demonstrated that circulating human peripheral blood T cells can express MHC class II (MHC-II) 3 determinants and that the frequency of these MHC-II ϩ CD4 T cells increases after T cell activation. The expression of MHC-II on activated T cells occurs in most mammalian species except for mice, as their T cells cannot transcribe CIITA that is required for MHC-II expression (3,4).…”