Back-to-back Science Sub-Journal: Are foreign immune cells good for infection?

Click the blue word to focus on our tissue-resident memory T cells (T-RM cells) are a new type of tissue-resident, long-term memory T cells that express CD69 and CD103 enriched on the cell surface
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Different transcriptomic characteristics exist with effector memory T cells
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Before entering tissues, T-RM cells undergo a transcriptionally programmed differentiation process that promotes their long-term residency
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Under antigenic stimulation, T-RM cells are rapidly activated, undergo cell proliferation, are in a local alert state, cause the recruitment of immune cells, and ultimately produce tissue-specific anti-infective responses
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In addition to the existence of peripheral tissues, T-RM cells also exist in the brain and blood-brain barrier
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T-RM cells are present in chronic inflammatory or autoimmune diseases such as asthma, psoriasis, vitiligo, inflammatory bowel disease and type 1 diabetes
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On April 13, 2022, the journal Science Translational Medicine published two articles back-to-back, revealing that T-RM cells depend on CD4 + helper T cells to participate in the pathological process of central nervous system immune system diseases
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The research team of Roland S.
Liblau of the University of Toulouse, France, showed a large number of T-RM cell infiltration in the brain of patients with autoimmune encephalitis, and further simulated autoreactive tissue-resident CD8 + T cells in a focal neurological autoimmune animal model.
site of neuroinflammation and cause progressive neuronal loss
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They found significant T-cell infiltration in the brains of patients with autoimmune encephalitis, of which about 60% were CD8-positive T-RM cells located close to neurons
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Orex-HA mice, a hypothalamic orexinergic neuron that selectively expresses the self-antigen hemagglutinin (HA), rapidly increased the number of CD8-positive T cells in the hypothalamic region following intravenous injection of HA-specific effector CD8-positive T cells The subsequent increase in expression of CD69 and CD103 was evident on day 8 post-injection, suggesting that CD8-positive T-RM cells reside in the hypothalamus
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Interestingly, there was marked neuronal loss in thalamic orexinergic neurons on day 8 post-injection
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Depletion of CD8-positive T cells in the peripheral blood of Orex-HA mice following T cell stimulation did not reduce the loss of hypothalamic neurons
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CD4+ helper T cells play an important role in T-RM cell development and maintenance
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Although early simultaneous depletion of peripheral CD8-positive T cells and CD4+ helper T cells did not prevent the differentiation of HA-specific effector CD8-positive T cells in the hypothalamus, there was a marked reduction in the number of hypothalamic T-RM cells, appetite and appetite after 1 month of depletion.
Primer neuron loss was also reduced, suggesting that hypothalamic-resident T-RM cells depend on CD4+ helper T cells for neuronal loss
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Lymphocytic choriomeningitis is an acute infectious disease caused by lymphocytic choriomeningitis virus (LCMV)
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At the same time, the research team of Doron Merkler at the University of Geneva, Switzerland, used LCMV to target self-antigens on brain astrocytes to induce an immune response, promote the increase in the number of resting T-RM cells, and cause motor dysfunction
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They found large numbers of T-RM cells in both the acute active phase in patients with multiple sclerosis and in patients with neuromyelitis optica spectrum disorder
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Depletion of peripheral CD8-positive T cells did not affect the expansion of T-RM cells, nor did it alter the dyskinesias of the mice
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However, after depletion of CD4 + helper T cells, the number of T-RM cells gradually decreased and could not proliferate and differentiate into a final effector state
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In general, the above two articles use different immune effector animal models to induce the residency of T-RM cells in the brain, and the emergence of local neuroimmune responses mimics neuroimmune disease states, and found that CD4 + helper T cells are T-RM cells.
Important cofactors that reside in the central nervous system
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【Reference】1.
Frieser et al.
, Sci.
Transl.
Med.
14, eabl6157 (2022), Tissue-resident CD8 + T cells drive compartmentalized and chronic autoimmune damage against CNS neurons2.
Vincenti et al.
, Sci.
Transl.
Med.
14, eabl6058 (2022) ,Tissue-resident memory CD8 + T cells cooperate with CD4 + T cells to drive compartmentalized immunopathology in the CNSThe picture in the text is from reference