CD4+ and CD8+ lymphocyte responses and cytokine profiles in visceral leishmaniasis patients following effective treatment in distinct transmission settings in Bihar, India
- 1Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
- 2Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
- 3QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Abstract
Visceral leishmaniasis (VL), caused by Leishmania donovani , is characterized by a complex immune response, with a dominant Th1 profile crucial for parasite elimination. This study aimed to assess the persistence of immune memory and cytokine responses in individuals with a history of VL, focusing on the activation and proliferative capacity of CCR7/CD45RA defined CD4 ⁺ and CD8 ⁺ lymphocyte populations corresponding to central memory-like and effector memory-like phenotypes. We examined three distinct groups from areas with different transmission histories: areas with no transmission (NT), areas with continuous transmission (CT), and areas experiencing an outbreak (OB). Using soluble Leishmania antigen (SLA)-stimulated whole blood assays and flow cytometry, we measured Th1, Th2, and Th17 cytokine levels, activation marker CD69 and proliferation marker Ki67 in CD4 ⁺ and CD8 ⁺ lymphocytes. SLA stimulation elicited significant increases in IFN-γ, IL-10 and IL-2 relative to unstimulated controls within the NT and OB groups and was not significant in CT group. In contrast, comparison of antigen specific responses among transmission settings demonstrated significantly lower ΔIL-10 response in the CT group, whereas ΔIFN-γ and ΔIL-2 responses were not significantly different. CD4 ⁺ CD45RA⁻CCR7 ⁺ , CD4 ⁺ CD45RA⁻CCR7⁻ CD8 ⁺ CD45RA⁻CCR7 ⁺ and CD8 ⁺ CD45RA⁻CCR7⁻ memory-phenotype lymphocyte subsets showed the higher absolute frequencies of activated cells in CT people, measured by expression of CD69, but not of proliferative responses. By contrast, the proliferation of CD4 ⁺ CD45RA⁻CCR7 ⁺ cells were increased in the OB group, underscoring variations in the functional nature of immunological memory between transmission circumstances. These findings indicate that while Th1 cytokine responses are preserved, the proliferative capacity of memory-phenotype lymphocytes varies by transmission setting, reflecting differences in antigen exposure and with implications for long-term protection and immune surveillance in VL elimination settings.
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BibTeX
@article{tiwari2026lymphocyte,
title = {{CD4+ and CD8+ lymphocyte responses and cytokine profiles in visceral leishmaniasis patients following effective treatment in distinct transmission settings in Bihar, India}},
author = {Rahul Tiwari and Siddharth Sankar Singh and Sarita Singh and Vishal Kumar Singh and Rajneesh and Vibhav Gautam and Christian Engwerda and Shyam Sundar and Rajiv Kumar},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1919529},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919529/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CD4+ and CD8+ lymphocyte responses and cytokine profiles in visceral leishmaniasis patients following effective treatment in distinct transmission settings in Bihar, India
AU - Rahul Tiwari
AU - Siddharth Sankar Singh
AU - Sarita Singh
AU - Vishal Kumar Singh
AU - Rajneesh
AU - Vibhav Gautam
AU - Christian Engwerda
AU - Shyam Sundar
AU - Rajiv Kumar
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1919529
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919529/full
AB - Visceral leishmaniasis (VL), caused by Leishmania donovani , is characterized by a complex immune response, with a dominant Th1 profile crucial for parasite elimination. This study aimed to assess the persistence of immune memory and cytokine responses in individuals with a history of VL, focusing on the activation and proliferative capacity of CCR7/CD45RA defined CD4 ⁺ and CD8 ⁺ lymphocyte populations corresponding to central memory-like and effector memory-like phenotypes. We examined three distinct groups from areas with different transmission histories: areas with no transmission (NT), areas with continuous transmission (CT), and areas experiencing an outbreak (OB). Using soluble Leishmania antigen (SLA)-stimulated whole blood assays and flow cytometry, we measured Th1, Th2, and Th17 cytokine levels, activation marker CD69 and proliferation marker Ki67 in CD4 ⁺ and CD8 ⁺ lymphocytes. SLA stimulation elicited significant increases in IFN-γ, IL-10 and IL-2 relative to unstimulated controls within the NT and OB groups and was not significant in CT group. In contrast, comparison of antigen specific responses among transmission settings demonstrated significantly lower ΔIL-10 response in the CT group, whereas ΔIFN-γ and ΔIL-2 responses were not significantly different. CD4 ⁺ CD45RA⁻CCR7 ⁺ , CD4 ⁺ CD45RA⁻CCR7⁻ CD8 ⁺ CD45RA⁻CCR7 ⁺ and CD8 ⁺ CD45RA⁻CCR7⁻ memory-phenotype lymphocyte subsets showed the higher absolute frequencies of activated cells in CT people, measured by expression of CD69, but not of proliferative responses. By contrast, the proliferation of CD4 ⁺ CD45RA⁻CCR7 ⁺ cells were increased in the OB group, underscoring variations in the functional nature of immunological memory between transmission circumstances. These findings indicate that while Th1 cytokine responses are preserved, the proliferative capacity of memory-phenotype lymphocytes varies by transmission setting, reflecting differences in antigen exposure and with implications for long-term protection and immune surveillance in VL elimination settings.
SN - 1664-3224
ER -