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Infection and Immunity, September 2001, p. 5635-5642, Vol. 69, No. 9
Department of Immunology, School of
Biological Sciences, Centre for Advanced Studies in Functional
Genomics,1 and Department of
Statistics, School of Mathematics,3 Madurai
Kamaraj University, Madurai 625 021, Government Hospital,
Singampunari 630 502,2 and TB
Sanatorium, Thoppur 625 006,4 India
Received 19 January 2001/Returned for modification 6 March
2001/Accepted 21 May 2001
HLA DRB1*02 and its subtypes predispose individuals for a
far-advanced sputum-positive pulmonary tuberculosis transcending ethnic
boundaries. Mycobacterium bovis BCG does not afford the desired protection against adult pulmonary tuberculosis, and a spectrum
of immune reactivity exists in controls and hospital contacts. All of
these findings have been identified and demonstrated in areas of
endemicity. Skewing of immunity from protective to pathogenic
may involve a shift in the Th1-Th2 paradigm. To elaborate these ideas,
we studied gamma interferon (IFN-
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.9.5635-5642.2001
Association of Interleukin-10 Cytokine Expression
Status with HLA Non-DRB1*02 and Mycobacterium bovis
BCG Scar-Negative Status in South Indian Pulmonary
Tuberculosis Patients
and
), interleukin-4 (IL-4), and IL-10
cytokine expression in 71 adult pulmonary tuberculosis patients and 74 controls from areas of endemicity in south India by 48-h microculture
and reverse transcription-PCR. Most of the patients and controls
expressed IFN- de novo, and in the presence of purified protein
derivative (PPD), all of them expressed significantly higher levels of
IFN-, suggesting a PPD-specific recall memory. HLA DRB1*
allele-dependent IFN- expression was identified only in controls,
suggesting a skewing of the immune response in patients. In contrast to
the case for IFN-, only some patients and controls expressed IL-4 or
IL-10 (Th2 profile); thus, the Th1 profile was identifiable only by a
nonexpression of IL-4 or IL-10 in this area of endemicity. The
Th2 profile was associated with HLA non-DRB1*02 and BCG scar-negative
status in patients, attributing a significant risk (odds ratio = 2.074; 95% confidence interval = 0.612 to 7.07). It is possible
that Mycobacterium tuberculosis (PPD)-specific IL-10 is
expressed preemptively in unvaccinated (BCG scar-negative) individuals
with a non-DR2 genetic background by chronic exposure in this area of
endemicity and leads to pulmonary tuberculosis of adults.
*
Corresponding author. Mailing address: Department of
Immunology, School of Biological Sciences, Centre for Advanced Studies in Functional Genomics, Madurai Kamaraj University, Madurai 625 021, India. Phone: (91) 452 858269. Fax: (91) 452 859181. E-mail: immunology{at}vsnl.com or pitchappan{at}netscape.net.
Present address: Department of Population Medicine and Diagnostic
Sciences, Cornell University, Ithaca, NY 14850.
Present address: Directorate of Medical Education, Chennai 600010, India.
Infection and Immunity, September 2001, p. 5635-5642, Vol. 69, No. 9
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.9.5635-5642.2001
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