Yes. humans treated with adoptively transferred T cells transduced to express a TCR specific for a tumor antigen like CD19 on CLL (chronic lymphocytic leukemia) cells become ill due to a condition call tumor lysis syndrome. This represents massive tumor cell lysis by the expanding adoptively transferred T cells. This illness therefore represents a good response. It is due to the release of intracellular contents (potassium, uric acid, etc) of the dying CLL cells. Pro-inflammatory cytokines (IL-1, IL-6, TNF) are also released by the T cells and likely contribute to the symptoms experienced by these patients. This would be consistent with weight loss since these cytokines are known to induce cachexia. Tumor lysis syndrome can be treated in humans to minimize the symptoms and the same should be possible with mice. There is good and exciting literature on the subject of adoptively transferred CART (chimeric T Cell Receptor) T cells that you should review. Hope this helps.

Thank you Richard.

As I said, I suspect that this is what is happening but I haven't formally shown it.

Perhaps a serum ELISA for IL-6 would help .

It seems, similar disorders may be observed in different T cell mediated pathologies. The most known is rant disease in mice with graft versus host reaction. Now we have transgenic mouse strain prone to develop cachexia. These mice express single beta chain derived from autoreactive TCR. In these mice we see normal development up to 1 month. Then, severe lymphopenia with almost full absence of thymus and lymph nodes (50-100x decrese) and cachexia develop. The level of glucose in blood is decreased. In thymus we see drastic decrease in percent of DP T cells. CD4-CD8 plots are very similar to ones for lymph nodes. CD4/CD8 ratio in thymus, LN and spleen is ~1 : 1. Cortical and medullary elements in thymus are mixed. In spleen borders between red and white pulpa are degraded. In spite of severe lymphopenia, T cells from lymph nodes develop normal immune responses in MLR. It is mysterious that we do not see any other disorders. After 4-6 months these mice die. We can not attribute complex of disorders to any exact mouse or human pathology. I think, this disease has some common features with ones developng in Pedro's mice. So, I would be very grateful to RG members for providing explanation.

Dear Dmitry, have you measured cytokine levels (IL-2, IFNg, TNF-a, IL-6, etc) in the serum of mice over-time? The signature of cytokines may give you an idea of which cell types are deregulated.

You would think no GvHD would develop in your mice (because of thymic selection) but you never know. Do the CD8 and CD4 cells express activation markers (CD69, Lag-3, low CD62L, absence of CD127, etc)? Are they proliferating faster than usual (BrdU incorpororation)? What happens if you transfer the T cells to secondary recipients, do you recapitulate the phenotype?

Dear Pedro, we did not detected cytokines in serum. We determined CD44 and CD62L on peripheral T cells and could see only slight increase in CD44loCD62Lhi (naive) T cells in the spleen as cmpared with wild type animals. Spontaneous proliferation in MLR cultures was not increased. So, we do not see clear evidences for autoimmune pathology or any activation of T cells. There is some positive correlation between the level of CD8+ T cells and the severity of disease, but no evidences for abnormal activation of CD8+ T cells.