1 research outputs found
Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis
Leishmania (Viannia) braziliensis induces American tegumentary leishmaniasis that
ranges in severity from the milder form, cutaneous (CL) to severe disseminated
cutaneous leishmaniasis. Patients with CL develop a cell-mediated Th1 immune
response accompanied by production of inflammatory cytokines, which contribute to
parasite control and pathogenesis of disease. Here, we describe the accumulation of
circulating T cells with multiple features of telomere dependent-senescence including
elevated expression of CD57, KLRG-1, and γH2AX that have short telomeres and low
hTERT expression during cutaneous L. braziliensis infection. This expanded population
of T cells was found within the CD45RA+CD27− (EMRA) subset and produced high
levels of inflammatory cytokines, analogous to the senescence-associated secretory
profile (SASP) that has been described in senescent non-lymphoid cells. There was
a significant correlation between the accumulation of these cells and the extent of
systemic inflammation, suggesting that they are involved in the inflammatory response
in this disease. Furthermore, these cells expressed high level of the skin homing
receptor CLA and there was a highly significant correlation between the number of
these cells in the circulation and the size of the Leishmania-induced lesions in the
skin. Collectively our results suggest that extensive activation during the early stages
of leishmaniasis drives the senescence of T cells with the propensity to home to the skin.
The senescence-related inflammatory cytokine secretion by these cells may control the
infection but also contribute to the immunopathology in the disease