Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary...

Area of Science:

• Immunology
• Infectious Diseases
• Microbiology

Background:

• Extrapulmonary tuberculosis (EPTB) disproportionately affects immunocompromised individuals.
• Immune phenotypes and activation patterns can persist post-recovery from EPTB.
• Understanding immune responses after EPTB may reveal factors influencing tuberculosis (TB) risk.

Purpose of the Study:

• To characterize immune responses in individuals with a history of EPTB compared to other TB-related conditions.
• To identify immune markers associated with susceptibility or resilience to EPTB.

Main Methods:

• Two case-control studies were conducted in the US and Brazil.
• Participants included individuals with prior EPTB, pulmonary TB, latent Mtb infection, and uninfected controls.
• Immune assessments involved measuring cytokine production (IFN-γ, TNF-α), T-cell proliferation, and regulatory T-cell (Treg) frequency and phenotype after Mtb antigen stimulation.

Main Results:

• Individuals with prior EPTB exhibited the highest frequency of intracellular cytokine production in response to Mtb antigens.
• Prior EPTB patients in Brazil showed the greatest CD4+ T-cell proliferation and highest CD39 expression on Tregs.
• Treated EPTB patients maintained high levels of Mtb-specific memory responses and active Tregs.

Conclusions:

• Despite developing enhanced adaptive immune responses, individuals with treated EPTB remain susceptible.
• Persistent high-frequency Mtb-specific memory responses and active Tregs are observed post-EPTB treatment.
• Immune characteristics after EPTB recovery may offer insights into TB pathogenesis and risk stratification.