Biologic basis for interleukin-1 in disease

A novel transcription factor, T-bet, directs Th1 lineage commitment.

Aucun gene HLA seul n'a ete identifie comme conferant un risque de maladie. Distinction et definition des sous-types DR4. Role de la 3eme region hypervariable de DRβ1. Relation entre risque de pemphigus et DW1eme et DRW6eme, et relation entre susceptibilite a la polyarthrite rhumatoide et un groupe d'epitopes trouves dans les sous-types non DW10 de DR4

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780301102

The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.

Epstein-Barr virus.

T lymphocytes respond to foreign antigens both by producing protein effector molecules known as lymphokines and by multiplying. Complete activation requires two signaling events, one through the antigen-specific receptor and one through the receptor for a costimulatory molecule. In the absence of the latter signal, the T cell makes only a partial response and, more importantly, enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation. Our current understanding at the molecular level of this modulatory process and its relevance to T cell tolerance are reviewed.

http://science.sciencemag.org/content/sci/248/4961/1349.full.pdf

A cell culture model for T lymphocyte clonal anergy

Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of Borrelia burgdorferi, the agent of Lyme disease, and the major histocompatibility complex class II allele DRB1*0401. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly related peptide epitopes. Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.

https://science.sciencemag.org/content/sci/281/5377/703.full.pdf

Identification of LFA-1 as a Candidate Autoantigen in Treatment-Resistant Lyme Arthritis

T CELLS that recognize self antigen are clonally deleted in the thymus—a maturation process that occurs in the context of histo-compatibility molecules and the T-cell receptor. The minor lymphocyte stimulation antigens (Mis) effect these deletions through interactions with the Vβ portion of the T-cell receptor, thus mimicking bacterial 'superantigens'. Intrigued by the fact that each known Mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (Mtv), we re-evaluated the linkage relationships between the two gene families. Here we report perfect concordance in inbred and recombinant inbred mice between the presence of four Mtv proviruses with the expression of Mls gene products. These data suggest a general model in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immuno-logical repertoire of common laboratory mice.

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice.

https://www.cell.com/immunity/pdf/S1074-7613(01)00210-2.pdf

Epstein-Barr Virus Transactivates the Human Endogenous Retrovirus HERV-K18 that Encodes a Superantigen

CD4+ T helper (Th) clones can be divided into interleukin 2 (IL-2)-secreting Th1 and IL-4-secreting Th2 cells. We show in the present report that these two Th subsets have different activation requirements for lymphokine production and proliferation: namely, cholera toxin (CT) as well as forskolin inhibit T cell receptor (TCR)-mediated IL-2 production and proliferation in Th1 cells, while the same reagents fail to block IL-4 production and proliferation in Th2 cells. In addition, CT and forskolin differentially influence the proto-oncogene mRNA expression in Th1 vs. Th2 cells after stimulation with Con A. Since both reagents lead to elevated levels of intracellular cAMP, it is likely that Th1 and Th2 cells differ in their sensitivity to an increase in cAMP. Our results indicate that the two Th subsets use different transmission signal pathways upon TCR-mediated activation.

/pdf/cholera-toxin-discriminates-between-t-helper-1-and-2-cells-2yb8uepjty.pdf

Cholera Toxin Discriminates Between T Helper 1 and 2 Cells in T Cell Receptor-Mediated Activation: Role of cAMP in T Cell Proliferation

Cell-mediated immunity includes both the generation of cytotoxic cells and initiation of delayed-type hypersensitivity (DTH). The resting T-cell population, before stimulation by antigen, already contains cells of the Lyl subclass that are programmed to initiate DTH (and helper function) but not cytotoxic responses, as well as Ly23 cells which can generate killer activity (and suppressive function) but not DTH. The central implication of these findings is that the broad division between humoral and cell-mediated immune responses does not precisely correspond to the division of labor among T-cell subclasses. The relative contribution of DTH-competent Lyl cells and cytotoxic Ly23 cells to the classical homograft response remains to be determined.

/pdf/cell-mediated-immunity-delayed-type-hypersensitivity-and-1uira63pva.pdf

Brigitte T. Huber

Papers

Identification of LFA-1 as a Candidate Autoantigen in Treatment-Resistant Lyme Arthritis

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice.

Epstein-Barr Virus Transactivates the Human Endogenous Retrovirus HERV-K18 that Encodes a Superantigen

Cholera Toxin Discriminates Between T Helper 1 and 2 Cells in T Cell Receptor-Mediated Activation: Role of cAMP in T Cell Proliferation

Cell-mediated immunity: delayed-type hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses.