T cell repertoire alterations of vascularized xenografts.

The role of T cells in the rejection of vascularized xenografts has been little explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterations in molecular interactions could impair the T cell response. Because the analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipients treated with a combination of cobra venom factor and cyclosporin A (CsA), to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rejected xenografts, compared with allografts. After withdrawal of CsA (on day 40), the analysis of V beta family expression and corresponding complementarity-determining region 3 lengths in rejected xenografts revealed a Gaussian pattern, in contrast to a much more restricted pattern in rejected allografts (p = 0.002), suggesting that, after withdrawal of CsA, all the underrepresented T cell clones are rapidly expanded in xenografts. These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high number of T cells, the rapid expression of markers of activation (IL-2 receptor alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts. Taken together, these results suggest that the intensity and diversity of the T cell response to xenografts could be stronger than the response to allografts in vivo.

Immunosuppression by D-isomers of HLA class I heavy chain (amino acid 75 to 84)-derived peptides is independent of binding to HSC70.

BACKGROUND: Peptides derived from the class I heavy chain were shown to modulate immune responses in vitro and in vivo. A peptide derived from HLA-B2702 (2702.75-84) inhibited differentiation of cytotoxic T cells as well as T cell and natural killer cell-mediated cytotoxicity in vitro. Peptide-mediated immunomodulation seemed to be independent of the MHC proteins expressed by responder and stimulator cells. In vivo studies in rodents demonstrated prolongation of heart and skin allograft survival after peptide therapy. Here, the correlation between the peptide's biological activity and its amino acid sequence was analyzed using peptides derived from amino acid 75-84 of several mouse, rat, and human MHC class I proteins as well as peptides with single amino acid substitutions in the 2702.75-84 sequence. METHODS: Peptides consisting of both L- and D-amino acids were tested for inhibition of murine and human T cell-mediated and lymphokine-activated killer cell-mediated cytotoxicity, binding to hsc70, and prolongation of heart allograft survival in vivo. RESULTS: Replacement of glutamic acid residue (E) at position 75 with valine (V) resulted in a peptide [2702.75-84(E>V)] with increased in vitro and in vivo activity but unchanged affinity for hsc70. Surprisingly, both L- and D-isomers of 2702.75-84 and 2702.75-84(E>V) inhibited cytotoxic cells in vitro and prolonged heart allograft survival in vivo. However, as expected, the peptides consisting of D-amino acids did not bind to hsc70. CONCLUSION: Assuming that both D- and L-isomers modulate immune responses by similar mechanisms, these results suggest that the peptides' effect is independent of binding to hsc70.

Shared HLA antigens between parents and recurrent spontaneous abortion.

Ten couples with a history of at least three (mean 3.8) consecutive spontaneous abortions of unknown etiology and 57 normal fertile couples (means 2.6 children) were tested for HLA antigens. The frequencies of shared HLA-A, -B and -DR antigens among members of the couples were similar in both groups. Our results, as well as analysis of the data in the literature, contradict HLA antigens sharing between parents as a determinant of recurrent spontaneous abortion.

Lymphocyte subpopulations in Spanish parenteral drug addicts.

Lymphocyte subpopulations were studied in 29 symptom-free Spanish prisoners who were active parenteral drug abusers. In 16/29 drug addicts (55%) the helper-inducer/suppressor-cytotoxic ratio (Leu 3a/Leu 2a) was less than 1. None of these 16 patients had lymphopenia and only 2 had a reduction in the number of Leu 3a cells. In drug addicts the number of lymphocytes (p less than 0.01) and the number and percentage of Leu 2a cells (p less than 0.001) were significantly raised. The addicts also had a higher absolute number of T cells when measured by their ability to react with the Leu 4 antibody (p less than 0.01). However, the E-rosette forming cells were significantly reduced. Thus the E-rosette test may lead to an overestimation of "null" cells. Furthermore drug addicts had a higher percentage (p less than 0.001) of Leu 7 positive cells (NK and K cells), but a normal percentage of B and phagocytic cells. Five drug addicts had generalized persistent lymphadenopathies, and 2 had skin anergy. We believe that most of the immunologic abnormalities seen in these apparently healthy drug abusers can be explained by an antigenic overload.

[Circulating immune complexes in treated latent syphilis]. / Complejos inmunes circulantes en sífilis latente tratada.

22 patients with treated latent syphilis were studied by the method of anticomplementary activity. The patients did not have any antecedent of primary or secondary muco-cutaneous lesion or any other clinical or humoral manifestation of other diseases. The presence of circulating immune complexes with statistical significance were shown in 14 cases. Syphilis in this period is considered as an immuno reactive disease, obliging to periodic clinical and specialized laboratory controls.