Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

Abstract

NZB mice develop a progressive autoimmune disease resembling human systemic lupus erythematosus (1-3) in many respects. The natural history of this disease is characterized by the development of hemolytic anemia, splenomegaly, glomerulonephritis, and numerous autoantibodies (4-5). Humoral immune responses to a number of antigens have been found to be abnormal in NZB mice (4-8) and induction of tolerance to soluble protein antigens to be more difficult in NZB than in other strains (9). A variety of mechanisms have been proposed for these abnormalities (10-14). In older mice, T-cell functions like mitogen responsiveness (15), graft-versus-host reactivity (16), and cell-mediated cytotoxicity (17-20) have generally been decreased, although in a recent report (21) the level of some of these functions in the NZB strain has been observed to be within the range of normal.In previous investigations (17-21) the phenomenon of cell-mediated lympholysis (CML) I in NZB mice has been examined by using targets differing at the major histocompatibility complex (MHC) from NZB or against virus-infected targets. In the experiments reported here, the primary in vitro CML activity of NZB mice was investigated against syngeneic targets and against targets carrying the NZB MHC type (H-2 d) on a background differing from NZB. In this situation primary in vitro CML activity is not generated by normal strains (22)(23)(24)(25)(26). In the present experiments a significant unidirectional CML was unexpectedly demonstrated against H-2 identical allogeneic targets by NZB effector cells. These results represent the first demonstration of a CML reaction in a primary in vitro system directed against unmodified targets which do not differ from the cytotoxic effectors in the MHC. They provide evidence for a qualitative difference in T-cell cytotoxic function between NZB mice and control

Primary cell-mediated lympholysis response to a maternally transmitted antigen.

“…1 A). The greater degree of lysis of BALB/c targets than of B6 targets is consistent with H-2-restricted, minor histocompatibility antigenspecific cytolysis, as reported by others (10,11,13). We confirmed that (NZB × B 10.D2)Fx anti-BALB/c CTL can also be generated in a primary response, and the the cytolysis was H-2-unrestricted, with lysis of both H-2 b targets tested (Fig.…”

“…In that report, the investigators did not detect Mtaspecific lysis in NZB primary CML responses. However, other investigators have reported H-2-unrestricted lysis of Qa-l a target cells by primary NZB CTL (10,11,13,14). We observed low levels of such lysis in approximately one-third of our NZB primary CML responses to H-2-compatible stimulators.…”

NZB cytotoxic lymphocyte responses. Kinetic analyses.

“…Recently, it has been reported that NZB spleen cells could generate a primary in vitro CTL response against unmodified non-NZB targets, which were identical to NZB mice in the major histocompatibility complex (i.e., H-2 d) (2,3). This phenomenon has been confirmed by others and found to be directed against Qa-1b-associated antigenic determinants (4) and, to a lesser extent, other minor locus determinants (U. Botzenhardt.…”

Increased Helper Cell Activity of NZB Mice against H-2-Identical Allogeneic Cells

“…Numerous abnormalities of their immune system are known, concerning both humoral and cel lular immune functions [1][2][3][4]. Among the T-cell dys functions, a unique hyperreactivity against H-2 iden tical cells of other mice has been described [5]. In con trast to normal mice, NZB recognizes and kills target cells of other H-2d mice in primary in vitro culture.…”

“…In con trast to normal mice, NZB recognizes and kills target cells of other H-2d mice in primary in vitro culture. Minor histocompatibility (MIH) antigens most likely are the structures triggering the response [5][6][7][8][9][10], Various possibilities for the cellular basis of this hyperreactivity have been proposed. It could be caused by isolated abnormalities of the effector cells involved or by dysfunctions of immunoregulatory cells or by combined defects [3,4,[11][12][13][14][15][16][17][18], especially 1 Supported by Deutsche Forschungsgemeinschaft (SFB 107, Mainz).…”