Do regulatory CD8+ T cells control autoreactive CD4+ T cells in the mouse model of human MS?
A very thought-provoking study from Mark Davis’ lab was recently published in the journal Nature. In it, the authors describe the existence of a specialized population of CD8 + T cells that prevented autoimmune brain inflammation( EAE ) in mice ā a human multiple sclerosis laboratory model.
Let’s examine the findings of the study. Both Fig. 1 and Figure 2 are rather unnecessary because they only display the time kinetics of blood CNS responses to autoantigen immunization ( Fig. ) for CD4 +, CD8 + and + T cells. 1 ) or the frequency of the TCR clonal and nbsp, as well as the sequencing’s distribution based on it( Fig. 2. What was the point of displaying them in the paper itself is unclear.
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The expanded clones of CD4 + or CD8 + T cells were then subjected to TCR specificities testing by the authors. With a MOG35 ā 55 I – Ab peptide ā MHC tetramer, four of these CD4 + TCRs expressed in human leukemia SKW // cells produced strong staining. & nbsp,
Curiously, none of the nine TCRs from CD8 + T cell clones expressed in a mouse tissue hybridoma 58 / cells are stimulated when co-cultured with bone-marrow-derived dendritic cells pulsed by peptides derived from the myelin protein( a total of 350 were tested ). Therefore, CD8 + T cell expansion was being driven by something other than myelin protein.
The authors used H2 Db yeast – pMHC libraries to determine epitope specificity for TCRs from CD8 + T cells. One positive control CD8 + TCR and six of the clonally expanded were used. Strong tetramer staining was present in two of the TCRs ā EAE6 and EAE7 ā but no matches were discovered in the mouse genome. They were referring to the surrogate peptides( SPs ) found in the Peptide Library Screen.
It’s interesting to note that the co-immunization of these SPs with myelin peptide prevented mice from developing brain inflammation. & nbsp,
More importantly, in vitro & nbsp, CD8 + T cells isolated from SP-immunized mice but not control, naive mice inhibited myelin-specific but non-omabumin-symbolic CD4 +& bbSp. & nbsp,
Furthermore, only a small portion of CD8 + CD44 ++ CD122 + T cells from SPs-immunized donor mice displayed inhibitory function in vitro and in vivo, but not Ly49 +. It should be noted that the use of the anti-Qa-1b antibody had no impact on the CD8’s ability to suppress Myelin-specific CD4 + T cells. In this study, the authors also examined CD8 + T cell reactivity to PTX( pertussis toxin ) or CFA( complete Freund’s adjuvant ) used in the EAE immunization protocol and discovered that Ly49 + fraction was not increased.
How can we sum up this paper, then? Focus on the + T cells first because they are extra and seem out of place. Second, no endogenous peptides that resembled the SPs on the library screen were discovered. Could it be derived from the microbiota? It appears that the authors did not take this possibility into account. Third, how do Ly49 + CD8 + T cells, which are specific to SPs, inhibit myelin-specific CD4 + T cells? Not lucid. In the context of brain inflammation, it does seem to be very specific to myelin-specific CD4 + T cells. Myelin peptides are visible to CD4 + T cells, but they do not appear to recognize them. Very perplexing, in fact. & nbsp,
The” memory-like” CD8 + T cells, like those found in the Qa – 1b-restricted population, have generally been known to suppress immune response. Simply put, this paper offers some fresh evidence in that direction. However, it is not a novel concept or observation, and I am unable to imagine how it could have found its way into the pages of nature without some novel mechanistic evidence. & nbsp,
