Topic Discussion: TIM molecules and Kidney Transplantation

TIM is "T cell immunoglobulin mucin". They are molecules that have shown to play a major role in immune responses. TIM 1,3 and 4 are the ones mainly noted in the literature.  TIM-1 and 3 are more on T cells and Tim-4 on Antigen presenting cells.

TIM 1:- Expression is on CD4+T cells, B cells, Mast cells and NK cells.  The proposed ligands for this molecule are TIM-4, IM3, and IgA and heavy chain to name a few.  The role in innate immunity is mediating clearance of apoptotic bodies and maintenance of peripheral tolerance.  In adaptive immunity, it increased th2 differentiation. Disease models include increased expression Asthma, MS, Sarcoidosis, and epithelial cells in AKI( also called KIM-1)

TIM3:- Expression on TH1 and Th17 cells, CD8+T cells and Antigen presenting cells.  Innate immunity wise limits macrophage expansion and modulates CD80 and CTLA-4 expression on antigen presenting cells.  It also helps in peripheral tolerance.  Disease models include T cells in chronic malignancy and infection.  Down regulated in Asthma and MS

TIM4:- Expression on dendritic cells and macrophages.  Ligands are TIM 1 and CD4+ t cells.  It up regulates Th2 responses and proliferation of activated T cells.  Disease model is food allergies and Asthma.

The TIM family is appearing as modulators of the immune system and helps in co stimulation of T cells. More will come about these molecules to improve our understanding of transplant immunology.


ref:
http://www.ncbi.nlm.nih.gov/pubmed/17331850
http://www.ncbi.nlm.nih.gov/pubmed/21906254
http://www.ncbi.nlm.nih.gov/pubmed/20536563
http://www.ncbi.nlm.nih.gov/pubmed/16938542

IN the NEWS:- TIM-1 + B cells? and B cell tolerance!

TIM-1 is a costimulatory molecule that regulates immune responses by modulating CD4⁺ T cell effector differentiation. A recent mice study in JCI showed that it is expressed mainly in B cell subpopulation.  And these TIM-1 positive cells that are B cells also produced IL-10. IL-10 is a very important regulatory molecule like Foxp3.  These B cells were  characterized as CD1d^hiCD5⁺. Some consider these as B cells that have regulatory function.  TIM-1⁺ B cells were highly enriched for IL-4 and IL-10 expression, promoted Th2 responses, and could directly transfer allograft tolerance. Prior studies have shown such cells in mice to help keep SLE quiet and inflammation under control. Perhaps, just like the T regs, there is a small but strong population that are present called B reg cells. Now studies so far have only found these in mice. Can this hold true in human studies is hard to tell yet. Perhaps! It will be important in the field of transplantation to sought this out as we move forward towards a better world of transplant tolerance. Why do some people have more tolerance than other? Perhaps its a Breg phenomenon.  The current study suggests that TIM-1 may be a novel therapeutic target for modulating the immune response and provide insight into the signals involved in the generation and induction of Bregs.


Check it out
http://www.ncbi.nlm.nih.gov/pubmed/21821911