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Changes in cellular response to mycobacterial antigens and cytokine production patterns in leprosy patients during multiple drug therapy
- Source :
- Immunology. 94:197-206
- Publication Year :
- 1998
- Publisher :
- Wiley, 1998.
-
Abstract
- Changes in Mycobacterium leprae-induced lymphoproliferative responses and mediator release by leprosy patients’ lymphocytes were followed during multiple drug therapy (MDT). At the time of diagnosis, multibacillary (MB) patients who did not develop reactions responded to both sonicated M. leprae and synthetic disaccharide coupled to bovine serum albumin (ND-BSA) antigens, but those who would later develop reactions did not respond, even in the presence of added cytokines. The paucibacillary (PB) group initially had high responses to sonicated M. leprae but no response to ND-BSA, even in the presence of added cytokines. In the first year of treatment, the supernatants of PB patients’ cell cultures contained factors that enhanced the phytohaemagglutinin (PHA) response of normal cells. In contrast, those MB patients who did not develop reactions at a later stage produced culture supernatants that were inhibitory. Interestingly, the MB patients who later developed reactions during treatment, and did not initially respond to M. leprae, produced supernatants containing enhancing factors, like those of the PB group. Later on in the treatment, all patients had the same patterns: when response to M. leprae decreased from its highest level, inhibitory factors were produced. Further studies revealed that the supernatants which inhibited the PHA response of normal cells contained the active form of transforming growth factor-β1 (TGF-β1), whatever the disease type or treatment status of the donor. These TGF-β1 levels correlated directly with the degree of inhibition. Similarly, supernatants that neither inhibited nor enhanced PHA responses contained the highest levels of interleukin-10 (IL-10), while those from treated patients that enhanced contained the lowest levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ). These cytokine correlations transcended the conventional disease classification, and imply that all patients pass through a sequence of patterns of immune response during treatment. These treatment-induced changes may explain occasional reports of response patterns at variance with the ‘immunological spectrum’ of leprosy. BB, borderlineBL, borderline lepromatousBT, borderline tuberculoidIFN-γ, interferon gammaIL-4, interleukin-4IL-10, interleukin-10MB, multibacillaryPB, paucibacillaryRT–PCR, reverse transcriptase–polymerase chain reactionLL, polar lepromatousTGF-β1, transforming growth factor-β1TT, tuberculoid.
- Subjects :
- Adult
Male
Adolescent
medicine.medical_treatment
Immunology
Cell Culture Techniques
Leprostatic Agents
Inflammation
Polymerase Chain Reaction
Immune system
Antigen
Interferon
Leprosy
medicine
Humans
Immunology and Allergy
Phytohemagglutinins
Child
Phytohaemagglutinin
Antigens, Bacterial
Lepromatous leprosy
biology
business.industry
Middle Aged
medicine.disease
Mycobacterium leprae
Drug Combinations
Cytokine
Cell culture
Leukocytes, Mononuclear
biology.protein
Cytokines
Female
medicine.symptom
business
Follow-Up Studies
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 13652567 and 00192805
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.doi.dedup.....9248ad37032d078ea1366826e9b4ecc5