Biomedical subjects

A M Termijtelen

Publications and source records attributed to A M Termijtelen.

3 recordsLinked to original sources

PubMed1990

Evidence for tumor necrosis factor-alpha involvement in the optimal induction of class I allospecific cytotoxic T cells.

We have investigated the functional interaction between IL-2 and TNF on the generation of alloreactive CTL. The study was performed by using primary mixed cultures of lymphocytes from a MHC-recombinant sibling identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. Our data show that MHC class I disparity can trigger the induction of TNF receptor without promoting significant TNF production. Addition of exogenous TNF at the sensitizing phase of the primary mixed lymphocyte reaction did not result in CTL activation. However, when simultaneously added with IL-2, TNF could promote an optimal induction of cytotoxic T cell generation. The enhanced lytic ability of MHC class-I primed CTL by TNF was associated with a selective up-regulation of Tac Ag and subsequent amplification of cell proliferation. Furthermore, TNF was also found to induce a considerable increase in IL-2-induced intracellular benzyloxycarbonyl-L-lysine thiobenzylester-esterase activity by MHC class I-primed cells. TNF did not affect the expression of LFA1, CD2, CD4, and CD8, molecules that are associated with CTL-target interactions, on responder cells. These results extend our earlier observations on the role of class I MHC molecules that may function to transduce activation signals and suggest that TNF may be a potent mediator involved in the IL-2-induced acquisition of optimal lytic competence by precursor cytotoxic T cells.

Antigens, CD↗

PubMed1988

Allogeneic T cell activation triggering by MHC class I antigens.

The role of MHC-encoded class I molecules in allogeneic activation and proliferation of human T lymphocytes was investigated. The study was performed by using primary mixed culture of lymphocytes from MHC recombinant siblings identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. The results indicate that such allogeneic combination is sufficient to trigger early activation steps within responder T cells without promoting a significant proliferation. After MHC class I allosensitization, a significant proportion of cells entered the cell cycle (G0----G1). The stimulatory potential of MHC class I Ag was further stressed by the specific induction on responder cells of IL-2R (22% T cell activation Ag positive). Under the same experimental conditions, transferrin receptor expression and IL-2 activity were not detectable. This is consistent with the low T cell proliferation. Exogenous rIL-1 did not improve IL-2 production and the subsequent T cell proliferation indicating that these two events were not associated with a defective accessory cell function involving IL-1 release. MHC class I disparity can also prime precursor CTL to differentiate into IL-2-dependent functional MHC restricted cytotoxic T cells. Conversely IFN-gamma had no effect. Addition to the culture of W6/32, a mAb specifically directed against a monomorphic determinant on human class I HLA-A, -B, and -C Ag was able to block all these activation events. These data clearly indicate a role of HLA class I Ag involvement in the early events triggering allogeneic T cell activation.

Antibodies, Monoclonal↗

PubMed1987

Constitutive and induced expression of the individual HLA-DR beta and alpha chain loci in different cell types.

The HLA-DR subregion of the human major histocompatibility complex encodes molecules involved in the regulation of the immune response. These HLA class II molecules are transmembrane heterodimers composed of an alpha and a beta chain. The polymorphic beta chains are encoded by multiple, highly homologous loci, whereas the alpha chain is encoded by a single, nonpolymorphic locus. HLA-DR is expressed constitutively on B lymphocytes and on activated T lymphocytes. It can also be induced by interferon-gamma on most nonlymphoid cells. In a quantitative study of the expression of the individual DR beta chain loci, we have investigated: the levels of mRNA transcripts of the two functional DR beta loci (beta I and beta III) in B cells of various haplotypes; whether both beta chain loci are expressed in activated T cells and, if so, the level of expression of each; whether both loci are expressed in interferon-gamma-induced nonlymphoid cells. This analysis relied on locus-specific DR beta chain oligonucleotide probes. Expression of both the beta I and the beta III loci was observed in all cell types and in all haplotypes tested. In every case the amount of beta I mRNA was about 5 times higher than that of beta III mRNA. This indicates a controlled and coordinated regulation of the mRNA levels of these two HLA-DR loci under all conditions of major histocompatibility complex class II gene expression.

B-Lymphocytes↗