PubMed Health⌕ Search

Biomedical subjects

T Mohanakumar

Publications and source records attributed to T Mohanakumar.

At least 181 records · Page 10Linked to original sources
PubMed1992

A polymorphic human kidney-specific non-MHC alloantigen. Its possible role in tissue-specific allograft immunity.

Tissue specific non-MHC alloantigens play a crucial role in allograft immunity. However, their structural properties have remained elusive, largely due to their inability to induce a strong antibody response. We report the characterization of a monkey heteroantiserum, MHK-I, raised against human kidney cells, that serologically reacts specifically with kidney cells after extensive absorptions of anti-HLA class I and II reactivities. The non-MHC MHK-I-binding molecule(s) is expressed only in the renal cortex on the glomerulus, peritubular capillaries, venous endothelium, and tubular epithelium. Immunochemically, MHK-I recognizes a kidney-specific non-MHC alloantigen of Mr 90,000 to 100,000 (90 kD). These properties of MHK-I are similar to those of the previously characterized alloantibodies eluted from rejected kidneys. These alloantibodies bind to the kidney from which the antibody was eluted and to a few others but are unlike MHK-I, which binds to extracts prepared from all human kidneys. Biochemical analysis by two-dimensional electrophoresis (pI ranging between 4.5 and 5.5) and peptide fingerprinting provide further evidence that the alloantigen is polymorphic. These findings imply that the non-MHC kidney-specific molecule(s) may function as target(s) for immune destruction of renal allografts.

Animals↗
PubMed1992

Selective loss of functional antidonor cytolytic T cell precursors following donor-specific blood transfusions in long-term renal allograft recipients.

Pretransplant administration of donor-specific blood transfusions prolongs the survival of HLA-disparate renal allografts to a level comparable to that of HLA-identical transplants. To test the hypothesis that DST recipients develop immunologic tolerance of their donors, we examined antidonor T cell immunity in a group of DST recipients with long-term well-functioning allografts. Limiting dilution analysis studies indicated that 5/14 long-term DST recipients exhibit a complete absence of detectable antidonor cytolytic T lymphocyte precursors (CTLp). In contrast, 4/4 long-term non-DST recipients who received conventional or cyclosporine immunosuppression exhibited significant levels of antidonor CTLp. Nonresponsive DST recipients retained the capacity to mount antidonor responses in mixed lymphocyte reactions and IL-2 production assays, and exhibited normal levels of CTLp directed to third-party antigens. Addition of exogenous IL-2 to cell-mediated lympholysis cultures did not restore antidonor CTL responses. In summary, our data suggest that the DST conditioning regimen induces a complete yet selective loss of functional antidonor CTLp in some long-term renal transplant recipients.

Blood Transfusion↗
PubMed1992

Immunogenicity of MHC class I alloantigens expressed on parenchymal cells in the human kidney.

The goal of the present study was to examine the capacity of human kidney cell lines (KCL) to elicit T cell responses to MHC class I alloantigens. KCL exhibited the phenotypic characteristics of tubular epithelial cells and were devoid of detectable contamination with leukocytes. Coculture of normal peripheral blood leukocytes (PBL) with allogeneic KCL elicited cytolytic T lymphocytes (CTL) that lysed the stimulating KCL but failed to lyse third-party KCL. Cell panel and antibody blocking studies demonstrated that the CTL were directed to the HLA class I alloantigens expressed on the KCL stimulators. Purified T cells completely failed to mount a CTL response to KCL, but the response could be reconstituted by supplementing the cultures with either autologous non-T cells or supernatant from a mixed lymphocyte culture (MLC). IL-2, but not IL-1, IL-4, IL-6, or gamma-interferon, restored the anti-KCL response, suggesting that IL-2 is the active factor in the MLC supernatant. Induction of class II antigens on the KCL stimulators with gamma-IFN failed to restore a CTL response, suggesting that KCL are deficient in a costimulatory factor important for class II restricted T helper responses. Nonetheless, our data demonstrate that parenchymal cells in the kidney are capable of presenting class I antigens to alloreactive T cells and, therefore, may contribute to the immunogenicity of renal allografts.

Cell Line↗
PubMed1991

Antiidiotypic antibodies to HLA class I alloantibodies in normal individuals: a mechanism of tolerance to noninherited maternal HLA antigens.

Recent reports indicate that 25%-50% of transplant patients exhibit B-cell nonresponsiveness to their noninherited maternal HLA antigens (NIMAs). To test the hypothesis that tolerance of NIMAs is mediated by antiidiotypic antibodies, sera from seven normal human subjects were tested for the capacity to inhibit the reactivity of HLA alloantisera directed to NIMAs. Five of seven sera inhibited (50%-100%) the cytotoxicity of monospecific alloantisera directed to their NIMAs. This inhibition was specific in that antisera directed to third-party HLA antigens were not inhibited. Cytotoxicity inhibition by normal sera was selective for antisera directed to HLA-B locus antigens. Absorption with an antibody specific for an HLA class I framework determinant eliminated the inhibitory activity of three of the five sera, suggesting that the inhibition was mediated by soluble HLA antigens in these cases. However, two of the sera retained inhibitory activity following soluble antigen depletion, suggesting that, in these cases, inhibition is mediated by antiidiotypic antibodies. This hypothesis was confirmed by purifying the immunoglobulin (Ig) fraction of one of these sera by anti-Ig affinity chromatography; the column eluate (Ig fraction) but not the effluent (Ig-depleted serum) was capable of inhibition. These data are consistent with the hypothesis that tolerance of NIMAs is mediated, at least in part, by antiidiotypic antibodies.

Antibodies, Anti-Idiotypic↗
PubMed1991

Immunology of renal allograft rejection.

Allograft rejection remains the critical problem of renal transplantation. The immunologic mechanisms that underlie renal allograft rejection are heterogeneous and involve the humoral and cellular limbs of the immune response. Antibody-mediated hyperacute rejection is now rare owing to improved prospective cross-matching. Chronic rejection, characterized by intrarenal arterial fibrosis, is still poorly understood. Knowledge of the afferent and efferent processes involved in rejection has led to effective therapeutic and experimental strategies that employ monoclonal antibodies and other pharmacologic agents to reverse, or prevent, acute allograft rejection. In addition, allospecific tolerance has been achieved experimentally and clinically in a variety of manners. Preliminary studies on the mechanism of allograft tolerance induced by donor-specific blood transfusions before transplantation suggest a role for an immunoregulatory cell population that specifically down regulates cytotoxic lymphocyte responses to donor antigens in some recipients. A role for noninherited maternal antigens and anti-idiotypic antibodies in down regulating immune responses to allografts have also been reported by several studies. An improved understanding of allograft rejection and tolerance may identify approaches to prolong allograft survival without the morbidity and mortality associated with present-day immunosuppression.

Animals↗
PubMed1990

Lack of T-cell tolerance of noninherited maternal HLA antigens in normal humans.

Recent clinical reports of nonresponsiveness to noninherited maternal human leukocyte antigens have led to speculation that humans may acquire tolerance of noninherited maternal antigens through exposure to maternal cells neonatally or in utero. To test this hypothesis, we measured the responsiveness of normal subjects to their noninherited maternal and paternal antigens using cell-mediated lympholysis assays and mixed leukocyte reactions. All individuals exhibited cell-mediated lympholysis and mixed leukocyte reaction responses to the maternal cells that were comparable to those to the paternal cells. Limiting dilution analyses revealed significant cytotoxic T-lymphocyte precursor frequencies to both sets of parental antigens. To exclude the possibility that tolerance of individual noninherited maternal antigens was masked by the response to other antigens expressed on the same target cell, we raised cytotoxic T lymphocytes to the maternal cells and then tested for reactivity to a panel of targets that expressed single noninherited maternal HLA antigens. In all cases, each noninherited maternal antigen expressed on the maternal cells elicited a significant cell-mediated lympholysis response. An analysis of clinical data showed that pretransplant mixed lymphocyte reactions to maternal cells are not significantly lower than those to paternal cells. These data suggest that the reported B-cell tolerance of noninherited maternal antigens is not mediated by clonal deletion of T cells induced by exposure to the maternal cells neonatally or in utero.

Adolescent↗